阅读说明：本技术 用于治疗癌症的组合物和方法 (Compositions and methods for treating cancer ) 是由 薇薇安·I·里贝尔 戴维·J·埃尔齐 威廉·E·鲍塔 于 2019-12-23 设计创作，主要内容包括：包含以下中的至少一种的双链RNA干扰(RNAi)试剂：(i)用于抑制CD320基因表达的第一双链核糖核酸(dsRNA),其中第一dsRNA包含形成双螺旋的有义链和反义链,(ii)用于抑制LRP2基因表达的第二dsRNA,其中第二dsRNA包含形成双螺旋的有义链和反义链,或(iii)：(i)和(ii)的混合物,并且其中第一dsRNA的有义链与第一dsRNA的反义链至少基本互补,并且第二dsRNA的有义链与第二dsRNA的反义链至少基本互补,和RNAi试剂作为治疗需要治疗的受试者中的癌症的药物组合物的用途。(A double-stranded RNA interference (RNAi) agent comprising at least one of: (i) a first double-stranded ribonucleic acid (dsRNA) for inhibiting expression of a CD320 gene, wherein the first dsRNA comprises a sense strand and an antisense strand forming a duplex, (ii) a second dsRNA for inhibiting expression of an LRP2 gene, wherein the second dsRNA comprises a sense strand and an antisense strand forming a duplex, or (iii): (i) and (ii) and wherein the sense strand of the first dsRNA is at least substantially complementary to the antisense strand of the first dsRNA and the sense strand of the second dsRNA is at least substantially complementary to the antisense strand of the second dsRNA, and the use of the RNAi agent as a pharmaceutical composition for treating cancer in a subject in need of treatment.)

1. A double-stranded RNA interference (RNAi) agent, comprising:

at least one of the following: (i) a first double-stranded ribonucleic acid (dsRNA) for inhibiting expression of a CD320 gene, wherein said first dsRNA comprises a sense strand and an antisense strand forming a duplex, (ii) a second dsRNA for inhibiting expression of an LRP2 gene, wherein said second dsRNA comprises a sense strand and an antisense strand forming a duplex, or (iii): (i) and (ii), and wherein the sense strand of the first dsRNA is at least substantially complementary to the antisense strand of the first dsRNA and the sense strand of the second dsRNA is at least substantially complementary to the antisense strand of the second dsRNA.

2. The double stranded RNAi agent of claim 1, wherein (i) the antisense strand of the first dsRNA comprises a region of complementarity to a CD320 RNA transcript.

3. The double stranded RNAi agent of claim 1, wherein (i) the sense strand of the first dsRNA is selected from table 5.

4. The double stranded RNAi agent of claim 1, wherein (i) the first dsRNA or (ii) the second dsRNA comprises a duplex region of 16-30 nucleotide pairs in length.

5. The double stranded RNAi agent of claim 1, wherein (i) the first dsRNA or (ii) the second dsRNA comprises a duplex region of 21-23 nucleotide pairs in length.

6. The double stranded RNAi agent of claim 1, wherein at least one strand of (i) the first dsRNA or (ii) the second dsRNA comprises a 3' overhang of at least 2 nucleotides.

7. The double stranded RNAi agent of claim 1, wherein (i) the antisense strand of the first dsRNA comprises a nucleotide sequence selected from the group consisting of (5'→ 3') seq id no:

CAGUUGCGCAGUUUCUUGUCAGUUCdTdT(SEQ ID NO:17)；

CAGUUGCGCAGUUUCUUGUCAGUUCdT*dT(SEQ ID NO 18)；

mCmAmGmUmUmGmCmGmCmAmGmUmUmUmCmUmUmGmUmCmAmGmUmU

mCdT*dT(SEQ ID NO 19)；

mCmAmGmUmUmGmCmGmCmAmGmUmUmUmCmUmUmGmUmCmAmGmUmU

mC(SEQ ID NO 21)；

mCmAmGmUmUmGmCmGmCmAmGmUmUmUmCmUmUmGmUmCmAmGmUmU

mCdT*dT(SEQ ID NO 23)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fUmU2fGmU2fCmA2fGmU2fU

mCdT*dT(SEQ ID NO 24)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fUmU2fGmU2fCmA2fGmU2fU

mC(SEQ ID NO 25)；

2fCmA2fGmU2fUmG2fCmG2fCmA2fGmU2fUmU2fCmU2fUmG2fUmC2fAmG2fUmU

2fCdT*dT(SEQ ID NO 28)；

2fCmA2fGmU2fUmG2fCmG2fCmA2fGmU2fUmU2fCmU2fUmG2fUmC2fAmG2fUmU

2fC(SEQ ID NO 29)；

mC2fA2fG2fU2fU2fG2fC2fG2fC2fA2fG2fU2fU2fU2fC2fU2fU2fG2fU2fC2fA2fG2fU2fU

2fCdT*dT(SEQ ID NO 30)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fUmU2fGmU2fCmA2fGmU2fU

mCdT*dT(SEQ ID NO 32)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fUmU2fGmU2fCmA2fGmU(SEQ ID NO 33)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fU2fU2fG2fU2fC2fA2fG2fU(SEQ ID NO 34)；

wherein mA, mC, mG and mU are respectively 2' -O-methyl adenylic acid, cytidine, guanosine or uridine; 2fA, 2fC, 2fG and 2fU are 2' -fluoroadenosine, cytidine, guanosine or uridine, respectively; and is a phosphorothioate bond; and

The sense strand is at least substantially complementary to the antisense strand.

8. The double stranded RNAi agent of claim 1, wherein (i) the antisense strand of the first dsRNA comprises a nucleotide sequence selected from the group consisting of (5'→ 3') seq id no:

AAGAGCUCAGGUCUCUGAGGGdTdT(SEQ ID NO 64)；

AAGAGCUCAGGUCUCUGAGGGdT*dT(SEQ ID NO 65)；

mAmAmGmAmGmCmUmCmAmGmGmUmCmUmCmUmGmAmGmGmGdT*dT(SEQ ID NO 66)；

mAmAmGmAmGmCmUmCmAmGmGmUmCmUmCmUmGmAmGmGmG(SEQ ID NO 68)；

mA2fAmG2fAmG2fCmU2fCmA2fGmG2fUmC2fUmC2fUmG2fAmG2fGmGdT*dT(SEQ ID NO 71)；

mA2fAmG2fAmG2fCmU2fCmA2fGmG2fUmC2fUmC2fUmG2fAmG2fGmG(SEQ ID NO 72)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fGdT*dT(SEQ ID NO 75)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fG(SEQ ID NO 76)；

mA2fA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fG(SEQ ID NO 77)；

mA2fA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fGdT*dT(SEQ ID NO 78)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fGdT*dT(SEQ ID NO 79)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fC2fU2fG2fA2fG2fG2fG(SEQ ID NO 81)；

wherein mA, mC, mG and mU are respectively 2' -O-methyl adenylic acid, cytidine, guanosine or uridine; 2fA, 2fC, 2fG and 2fU are 2' -fluoroadenosine, cytidine, guanosine or uridine, respectively; and is a phosphorothioate bond; and

the sense strand is at least substantially complementary to the antisense strand.

9. The double stranded RNAi agent of claim 1, wherein (i) the sense strand of the first dsRNA is no more than 30 nucleotides in length, and (i) the antisense strand of the first dsRNA is no more than 30 nucleotides in length.

10. The double stranded RNAi agent of claim 1, wherein the antisense strand of (ii) the second dsRNA comprises a region of complementarity to an LRP2 RNA transcript.

11. The double stranded RNAi agent of claim 1, wherein (ii) the antisense strand and the sense strand of the second dsRNA are selected from table 6.

12. The double stranded RNAi agent of claim 1, wherein (ii) the antisense strand of the second dsRNA comprises a nucleotide sequence selected from (5'→ 3') of:

UUUGAUAGCACCAAACCUAGAGCCCdTdT(SEQ ID NO:417)；

UUUGAUAGCACCAAACCUAGAGCCCdT*dT(SEQ ID NO:418)；

mUm[mUmGmAmUmAmGmCmAmCmCmAmAmAmCmCmUmAmGmAmGmCmCmC

dT*dT(SEQ ID NO:419)；

mUmUmUmGmAmUmAmGmCmAmCmCmAmAmAmCmCmUmAmGmAmGmCmCmC(SEQ ID NO:421)；

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fCmC2fUmA2fGmA2fGmC2fCmCdT*dT](SEQ ID NO:424)；

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fCmC2fUmA2fGmA2fGmC2fCmC(SEQ ID NO:425)；

mU2fAmU2fCmA2fAmA2fCmC2fUmC2fGmA2fUmA2fGmC2fAmA2fCmA2fCmC2fGmC(SEQ ID NO:429)；

mU2fU2fU2fG2fA2fU2fA2fG2fC2fA2fC2fC2fA2fA2fA2fC2fC2fU2fA2fG2fA2fG2fC2fC2fCdT*dT(SEQ ID NO:430)；

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fCmC2fUmA2fGmA2fGmC2fCmCdT*dT(SEQ ID NO:432)；

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fCmC2fUmA2fGmA2fGmC (SEQ ID NO: 433); and

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fC2fC2fU2fA2fG2fA2fG2fC(SEQ ID NO:434)

wherein mA, mC, mG and mU are respectively 2' -O-methyl adenylic acid, cytidine, guanosine or uridine; 2fA, 2fC, 2fG and 2fU are 2' -fluoroadenosine, cytidine, guanosine or uridine, respectively; and is a phosphorothioate bond; and

the sense strand is at least substantially complementary to the antisense strand.

13. The double stranded RNAi agent of claim 1, wherein (ii) the antisense strand of the second dsRNA comprises a nucleotide sequence selected from (5'→ 3') of:

UUUGCAAUGACUCUCCUAUCAGUCCdTdT(SEQ ID NO:448)；

UUUGCAAUGACUCUCCUAUCAGUCCdT*dT(SEQ ID NO:449)；

mUmUmUmGmCmAmAmUmGmAmCmUmCmUmCmCmUmAmUmCmAmGmUmCmCdT*dT(SEQ ID NO:450)；

mUmUmUmGmCmAmAmUmGmAmCmUmCmUmCmCmUmAmUmCmAmGmUmCmC(SEQ ID NO:452)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU2fCmCdT*dT(SEQ ID NO:455)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU2fCmC(SEQ ID NO:456)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fCmU2fC

mC(SEQ ID NO:458)；

2fUmU2fUmG2fCmA2fAmU2fGmA2fCmU2fCmU2fCmC2fUmA2fUmC2fAmG2fUmC2fCdT*dT(SEQ ID NO:459)；

mU2fAmU2fCmC2fUmA2fAmG2fUmC2fAmC2fAmC2fGmU2fUmU2fGmA2fCmU2fGmC(SEQ ID NO:460)；

mU2fU2fU2fG2fC2fA2fA2fU2fG2fA2fC2fU2fC2fU2fC2fC2fU2fA2fU2fC2fA2fG2fU2fC2fCdT*dT(SEQ ID NO:461)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU2fCmCdT*dT(SEQ ID NO:463)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU(SEQ ID NO:464)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fC2fU2fA2fU2fC2fA2fG2fU(SEQ ID NO:465)

wherein mA, mC, mG and mU are respectively 2' -O-methyl adenylic acid, cytidine, guanosine or uridine; 2fA, 2fC, 2fG and 2fU are 2' -fluoroadenosine, cytidine, guanosine or uridine, respectively; and is a phosphorothioate bond; and

the sense strand is at least substantially complementary to the antisense strand.

14. The double stranded RNAi agent of claim 1, wherein (ii) the sense strand of the second dsRNA is no more than 30 nucleotides in length, and the antisense strand is no more than 30 nucleotides in length.

15. The double stranded RNAi agent of claim 1, comprising (iii): (i) a combination of the first dsRNA and (ii) the second dsRNA.

16. The double stranded RNAi agent of claim 15, wherein (i) the antisense strand of the first dsRNA is selected from the group consisting of

CAGUUGCGCAGUUUCUUGUCAGUUCdTdT(SEQ ID NO:17)；；

CAGUUGCGCAGUUUCUUGUCAGUUCdT*dT(SEQ ID NO 18)；；

AAGAGCUGAGGUCUCUGAGGGGdTdT (SEQ ID NO 64); (ii) a And

aagagcucaggucugagggdt dT (SEQ ID NO 65); and

(ii) the antisense strand of the second dsRNA is selected from

UUUGAUAGCACCAAACCUAGAGCCCdTdT(SEQ ID NO:417)；；

UUUGAUAGCACCAAACCUAGAGCCCdT*dT(SEQ ID NO:418)；；

UUGCAAUGACUCUCCUAUCAGUCCdT (SEQ ID NO: 448); (ii) a And

UUUGCAAUGACUCUCCUAUCAGUCCdT*dT(SEQ ID NO:449)；

wherein is a phosphorothioate bond; and

the sense strand is at least substantially complementary to the antisense strand.

17. The double stranded RNAi agent of claim 1, wherein (i) the first dsRNA has the double helix structure of (SEQ ID NOs 17 and 110) or (SEQ ID NOs 18 and 111).

18. The double stranded RNAi agent of claim 1, wherein (ii) the second dsRNA has the double helix structure of (SEQ ID NOs 417 and 808) or (SEQ ID NOs 448 and 822).

19. An isolated cell comprising the double stranded RNAi agent of claim 1.

20. A pharmaceutical composition for inhibiting the expression of CD320 gene, comprising the double stranded RNAi agent (i) or (iii) of claim 1.

21. A pharmaceutical composition for inhibiting expression of LRP2 gene, the composition comprising the double stranded RNAi agent (ii) or (iii) of claim 1.

22. The pharmaceutical composition of claim 20, further comprising an excipient.

23. The pharmaceutical composition of claim 21, further comprising an excipient.

24. A method for inhibiting proliferation of a Cancer Cell (CC), comprising contacting the CC with an inhibitor of CD320 in an amount effective to inhibit proliferation of the CC.

25. The method of claim 24, wherein the CC expresses CD 320.

26. The method of claim 24, wherein the CC is from a cancer selected from the group consisting of: melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular carcinoma, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

27. The method of claim 24, wherein the inhibitor is selected from the group consisting of an antibody that binds CD320, a small molecule inhibitor of CD320, and an RNAi agent that hybridizes to a nucleic acid encoding CD 320.

28. A method of treating a treatment-resistant cancer in a subject previously receiving therapy, comprising administering to the subject an inhibitor of CD320 in an amount effective to inhibit or kill Cancer Cells (CCs) present in the treatment-resistant cancer.

29. The method of claim 28, wherein the CC expresses CD 320.

30. The method of claim 28, wherein the CC is from a cancer selected from the group consisting of: melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular carcinoma, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

31. The method of claim 28, wherein the inhibitor is selected from the group consisting of an antibody that binds CD320, a small molecule inhibitor of CD320, and an RNAi agent that hybridizes to a nucleic acid sequence encoding CD 320.

32. A method for treating cancer in a subject with recurrent or recurrent cancer, comprising administering to the subject an inhibitor of CD320 in an amount effective to inhibit or kill CC in the cancer.

33. The method of claim 32, wherein the CC expresses CD 320.

34. The method of claim 32, wherein the CC is from a cancer selected from the group consisting of: melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular carcinoma, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

35. The method of claim 32, wherein the inhibitor is selected from the group consisting of an antibody that binds CD320, a small molecule inhibitor of CD320, and an RNAi agent that hybridizes to a nucleic acid sequence encoding CD 320.

36. The method of any one of claims 27, 31, and 35, wherein the method further comprises administering a cancer therapeutic selected from the group consisting of: antifolates, epigenetic modulators or small molecule or protein inhibitors of CD320 function, such as antibodies.

37. The method of any one of claims 27, 31, and 35, wherein the method further comprises administering a cancer therapeutic in conjunction with the RNAi agent that hybridizes to mRNA encoding CD 320.

38. The method of any one of claims 27, 31, and 35, wherein the method further comprises administering a cancer therapeutic selected from the group consisting of: antifolates, epigenetic modulators (e.g., HDAC inhibitors), or small molecule or protein inhibitors of CD320 function, such as antibodies.

39. The method of any one of claims 27, 31, and 35, wherein the method further comprises administering metformin in conjunction with an RNAi agent that hybridizes to mRNA encoding CD 320.

40. The method of any one of claims 27, 31, and 35, wherein the RNAi agent comprises an antisense strand of table 5.

41. The method of any one of claims 27, 31, and 35, wherein the method further comprises administering an RNAi agent that hybridizes to mRNA encoding LRP2 in conjunction with the RNAi agent that hybridizes to a nucleic acid sequence encoding CD 320.

42. A method for inhibiting proliferation of a Cancer Cell (CC), comprising contacting the CC with an inhibitor of LRP2 in an amount effective to inhibit proliferation of the CC.

43. The method of claim 42, wherein the CC expresses LRP 2.

44. The method of claim 42, wherein the CC is from a cancer selected from the group consisting of: melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular carcinoma, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

45. The method of claim 42, wherein the inhibitor is selected from the group consisting of an antibody that binds LRP2, a small molecule inhibitor of LRP2, and an RNAi agent that hybridizes to a nucleic acid sequence encoding LRP 2.

46. A method for treating a treatment-resistant cancer in a subject who has previously received therapy comprising administering to the subject an inhibitor of LRP2 in an amount effective to inhibit or kill Cancer Cells (CCs) present in the treatment-resistant cancer.

47. The method of claim 46, wherein the CC expresses LRP 2.

48. The method of claim 46, wherein the CC is from a cancer selected from the group consisting of: melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular carcinoma, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

49. The method of claim 46, wherein the inhibitor is selected from the group consisting of an antibody that binds LRP2, a small molecule inhibitor of LRP2, and an RNAi agent that hybridizes to a nucleic acid sequence encoding LRP 2.

50. A method for treating cancer in a subject with recurrent or relapsed cancer comprising administering to the subject an inhibitor of LRP2 in an amount effective to inhibit or kill CC in the cancer.

51. The method of claim 50, wherein the CC expresses LRP 2.

52. The method of claim 50, wherein the CC is from a cancer selected from the group consisting of: melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular carcinoma, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

53. The method of any one of claims 42, 46, and 50, wherein the inhibitor is selected from the group consisting of an antibody that binds LRP2, a small molecule inhibitor of LRP2, and an RNAi agent that hybridizes to a nucleic acid sequence encoding LRP 2.

54. The method of any one of claims 42, 46, and 50, wherein the method further comprises administering a cancer therapeutic selected from the group consisting of: antifolates, epigenetic modulators or small molecule or protein inhibitors of LRP2 function, such as antibodies.

55. The method of any one of claims 42, 46, and 50, wherein the method further comprises administering a cancer therapeutic in combination with an RNAi agent that hybridizes to mRNA encoding LRP 2.

56. The method of any one of claims 42, 46, and 50, wherein the method further comprises administering a cancer therapeutic selected from the group consisting of: antifolates, epigenetic modulators (e.g., HDAC inhibitors), or small molecule or protein inhibitors of LRP2 function, such as antibodies.

57. The method of any one of claims 42, 46, and 50, wherein the method further comprises administering metformin in combination with an RNAi agent that hybridizes to mRNA encoding LRP 2.

58. The method of any one of claims 42, 46, and 50, wherein the RNAi agent comprises an antisense strand and a sense strand from Table 6.

59. A method for inhibiting proliferation of a Cancer Cell (CC), comprising contacting the CC with a composition comprising an inhibitor of CD320 and an inhibitor of LRP2 in amounts effective to inhibit proliferation of the CC.

60. The method of claim 59, wherein the CC expresses CD320 and LRP 2.

61. The method of claim 59, wherein the CC is from a cancer selected from the group consisting of: melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, kidney cancer, hepatocellular carcinoma, pancreatic cancer, ovarian cancer, and prostate cancer.

62. The method of claim 59, wherein the composition is a mixture comprising: i) a CD320 inhibitor selected from the group consisting of an antibody that binds CD320, a small molecule inhibitor of CD320, and an RNAi agent that hybridizes to a nucleic acid encoding CD320, and any combination thereof, and ii) an LRP2 inhibitor selected from the group consisting of an antibody that binds LRP2, a small molecule inhibitor of LRP2, and an RNAi agent that hybridizes to a nucleic acid sequence encoding LRP2, and any combination thereof.

63. The method of any one of claims 62, wherein the method further comprises administering a cancer therapeutic selected from the group consisting of: antifolates and epigenetic regulators.

64. The method of claim 62, wherein the RNAi agent that hybridizes to mRNA encoding CD320 comprises a first double-stranded ribonucleic acid (dsRNA) for inhibiting expression of CD320, wherein the first dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to a CD320 RNA transcript, and the RNAi agent that hybridizes to mRNA encoding LRP2 comprises a second dsRNA for inhibiting expression of LRP2, wherein the second dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to an LRP2 RNA transcript.

65. The method of claim 64, wherein the antisense strand complementary to a CD320 RNA transcript is selected from Table 5 and the antisense strand complementary to an RNA transcript of LRP2 is selected from Table 6.

66. The method of claim 62, wherein the method further comprises administering a cancer therapeutic selected from the group consisting of: antifolates and epigenetic regulators.

67. The method of claim 62, wherein the method further comprises administering a cancer therapeutic selected from the immunomodulatory class.

68. The method of claim 62, further comprising administering metformin.

Background

There are a variety of cancer therapies and treatments, such as surgical resection of solid tumors, radiation therapy, and chemotherapy. Despite the use of surgical resection and radiation therapy for localized tumors, chemotherapy is often delivered systemically and affects both cancerous and non-cancerous cells, resulting in serious and even life threatening side effects. Older cancer drugs, including alkylating agents, nucleotide antimetabolites, and tubulin toxicants (tubulin poisons), caused significant side effects because their toxicity to normal cells was similar to that to cancer cells, particularly those undergoing normal cell division in the intestine, scalp, and skin. To this end, much of the work in modern Cancer Drug Discovery has been devoted to finding targeted therapeutics that distinguish between Cancer cells and normal cells (novel et al, (2014) Cancer Drug Design and Discovery). This has led to the production of drugs that inhibit the function of oncolytic proteins that are mutated, overexpressed, or abnormally high activity in cancer, but do not have the above-described characteristics in normal cells. Examples of such drugs include kinase inhibitors, histone deacetylase inhibitors, proteasome inhibitors, mTOR inhibitors, BCL2 inhibitors, and isocitrate dehydrogenase inhibitors. Much work has also been devoted to targeting cell surface antigens that are differentially expressed in cancer cells compared to normal cells. Thus, monoclonal antibodies and antibody-Drug conjugates targeting cancer cell surface antigens have been developed as cancer therapeutics (Beck et al, (2017) Nat Rev Drug Disc 16, 315-. Another difference between cancer cells and normal cells is metabolism. It has been discovered many years ago that various cancer cells utilize glucose fermentation to produce ATP, in contrast to the oxidative phosphorylation process used by normal cells. Recently, the FDA approved Drugs targeting isocitrate dehydrogenase, which is involved in abnormal glucose metabolism in cancer cells (Dhillon (2018) Drugs 78, 1509-1516). Abnormalities in single carbon metabolism that encompass the folate and methionine cycle and affect nucleotide synthesis and DNA methylation as a way to control gene expression are strongly associated with some cancers (Fanidi et al, (2019) Int J Cancer 145, 1499-. In this regard, it has long been known that certain synthetic analogs of folic acid (antifolates) can inhibit the growth of cancer cells. It is also known that the survival of some cancer cells is dependent on the amino acid methionine. If methionine is restricted, cancer cells die, although this has little effect on normal cells. In recent years, some indications have begun to appear: some cancer cells may have an abnormal dependency on vitamin B12. The nature of this dependence is not understood, but may be partly related to the use of vitamin B12 as a catalytic cofactor in single carbon metabolism by the enzyme methionine synthase.

Vitamin B12 (cobalamin) is an essential micronutrient in the human diet. It is a cofactor for the metabolic enzymes methionine synthase and methylmalonate monoacyl-CoA mutase (Fedosov et al, (2012) Water solvent Vitamins (book)56, 347-367). After oral ingestion and intestinal delivery, cobalamin becomes a protein in plasma that binds almost completely to the chaperone transcobalamin protein 1(TCN1, corrin-binding protein (haptocorrin), R-binding protein) (TCO1_ HUMAN) and transcobalamin protein 2(TCN2) (TCO2_ HUMAN). Most cells use receptor-mediated endocytosis to take up the TCN 2-cobalamin complex (TCN2-Cbl) and have a plasma half-life of 1-15 h. TCN2 has high affinity and specificity for cobalamins such as methylcobalamin, adenosylcobalamin and cyanocobalamin in the form of their various dietary and nutritional supplements (Fedosov et al, (2007) Biochem 46, 6446-. TCN1 is a glycoprotein present in plasma in two different forms (Marzolo and Farfan (2011) Biol Res 44, 81-105). The most abundant form is sialylated and has a plasma half-life of about 10 days (Bor (2004) Clin Chem 50, 1043-. A lesser amount is desialylated and has a plasma half-life of several minutes. Unlike TCN2-Cbl, which can be taken up by almost all cell types, only the transcobalamin protein 1-cobalamin complex in its desialylated form (TCN1-Cbl) is taken up rapidly by certain liver cells by receptor-mediated endocytosis.

CD320 and LRP2 are two receptors involved in cobalamin uptake as TCN 2-Cbl. CD320 is a member of the Low Density Lipoprotein Receptor (LDLR) family, which is constitutively expressed in most cells and is the receptor primarily responsible for cobalamin uptake (Quadros (2013) Biochimie 95, 1008-1018). CD320 is overexpressed in some cancer types (Sycel et al, (2013) Anticancer Res 33, 4203-4212; Amagasaki (1990) Blood 76, 1380-1386). There is also evidence that: CD320 facilitates the transport of TCN2-Cbl across the blood-brain barrier to the brain (Lai et al; (2013) FASEB 27, 2468-. LRP2 is another receptor in the LDLR family. It is expressed most in the kidney, but also in other tissues. In addition to cobalamin, LRP2 also delivers a variety of proteins and small molecules, including albumin, insulin, and vitamin D (Mazolo et al, (2011) Biol Res 44, 89-105). In the liver, the asialoglycoprotein receptor (ASGR) takes up TCN1-Cbl by receptor-mediated endocytosis as long as TCN1 is in its desialylated form. Normal hepatocytes and liver cancer cells express extremely high levels of ASGR (-50,000 receptors per cell), which makes this receptor an attractive entry for drug delivery to the liver (Luo et al, (2017) Biomedicine and Pharmacotherapy 88, 87-94; Stockert (1995) Physiological Rev 75, 595-609; Soda et al, Blood (1985)65, 795-802).

Following receptor-mediated endocytosis, cobalamin is sequestered in the endosome, where the endosomal membrane prevents passive efflux into the cytosol. The specialized protein (cblF) facilitates transport of cobalamin across the endosomal membrane into the cytosol (Banerjee et al, (2009) Curr Opin Chem Bio 13, 484-491).

Disclosure of Invention

One embodiment of the invention provides a double-stranded RNA interference (RNAi) agent comprising at least one of: (i) a first double-stranded ribonucleic acid (dsRNA) for inhibiting expression of a CD320 gene, wherein the first dsRNA comprises a sense strand and an antisense strand forming a duplex, (ii) a second dsRNA for inhibiting expression of an LRP2 gene, wherein the second dsRNA comprises a sense strand and an antisense strand forming a duplex, or (iii): (i) and (ii) and wherein the sense strand of the first dsRNA is at least substantially complementary to the antisense strand of the first dsRNA and the sense strand of the second dsRNA is at least substantially complementary to the antisense strand of the second dsRNA. For example, (i) the antisense strand of the first dsRNA comprises a region of complementarity to a CD320 RNA transcript and, for example, (i) the sense strand of the first dsRNA is selected from table 5. (ii) The antisense strand of the second dsRNA comprises a region of complementarity to the LRP2RNA transcript and (ii) the sense strand of the second dsRNA is selected from table 6. In one example, (i) the first dsRNA or (ii) the second dsRNA comprises a duplex region that is 16-30 nucleotide pairs in length. In another example, (i) the first dsRNA or (ii) the second dsRNA comprises a duplex region of length 21-23 nucleotide pairs. In one embodiment, a double stranded RNAi agent comprises at least one strand of: a 3' overhang comprising at least 2 nucleotides (i) a first dsRNA or (ii) a second dsRNA. Further, in one embodiment, (i) the antisense strand of the first dsRNA comprises a nucleotide sequence selected from the group consisting of (5'→ 3') seq id no:

CAGUUGCGCAGUUUCUUGUCAGUUCdTdT(SEQ ID NO:17)；

CAGUUGCGCAGUUUCUUGUCAGUUCdT*dT(SEQ ID NO 18)；

mCmAmGmUmUmGmCmGmCmAmGmUmUmUmCmUmUmGmUmCmAmGmUmU

mCdT*dT(SEQ ID NO 19)；

mCmAmGmUmUmGmCmGmCmAmGmUmUmUmCmUmUmGmUmCmAmGmUmU

mC(SEQ ID NO 21)；

mCmAmGmUmUmGmCmGmCmAmGmUmUmUmCmUmUmGmUmCmAmGmUmU

mCdT*dT(SEQ ID NO 23)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fUmU2fGmU2fCmA2fGmU2fU

mCdT*dT(SEQ ID NO 24)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fUmU2fGmU2fCmA2fGmU2fU

mC(SEQ ID NO 25)；

2fCmA2fGmU2fUmG2fCmG2fCmA2fGmU2fUmU2fCmU2fUmG2fUmC2fAmG2fUmU

2fCdT*dT(SEQ ID NO 28)；

2fCmA2fGmU2fUmG2fCmG2fCmA2fGmU2fUmU2fCmU2fUmG2fUmC2fAmG2fUmU

2fC(SEQ ID NO 29)；

mC2fA2fG2fU2fU2fG2fC2fG2fC2fA2fG2fU2fU2fU2fC2fU2fU2fG2fU2fC2fA2fG2fU2fU

2fCdT*dT(SEQ ID NO 30)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fUmU2fGmU2fCmA2fGmU2fUmCdT*dT(SEQ ID NO 32)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fUmU2fGmU2fCmA2fGmU(SEQ ID NO 33)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fU2fU2fG2fU2fC2fA2fG2fU(SEQ ID NO 34)；

Wherein mA, mC, mG and mU are respectively 2' -O-methyl adenylic acid, cytidine, guanosine or uridine; 2fA, 2fC, 2fG and 2fU are 2' -fluoroadenosine, cytidine, guanosine or uridine, respectively; and is a phosphorothioate bond; and

the sense strand is at least substantially complementary to the antisense strand.

In another embodiment, the double stranded RNAi agent comprises (i) an antisense strand of the first dsRNA comprising a nucleotide sequence selected from the group consisting of (5'→ 3') seq id no:

AAGAGCUCAGGUCUCUGAGGGdTdT(SEQ ID NO 64)；

AAGAGCUCAGGUCUCUGAGGGdT*dT(SEQ ID NO 65)；

mAmAmGmAmGmCmUmCmAmGmGmUmCmUmCmUmGmAmGmGmGdT*dT(SEQ ID NO 66)；

mAmAmGmAmGmCmUmCmAmGmGmUmCmUmCmUmGmAmGmGmG(SEQ ID NO 68)；

mA2fAmG2fAmG2fCmU2fCmA2fGmG2fUmC2fUmC2fUmG2fAmG2fGmGdT*dT(SEQ ID NO 71)；

mA2fAmG2fAmG2fCmU2fCmA2fGmG2fUmC2fUmC2fUmG2fAmG2fGmG(SEQ ID NO 72)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fGdT*dT(SEQ ID NO 75)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fG(SEQ ID NO 76)；

mA2fA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fG(SEQ ID NO 77)；

mA2fA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fGdT*dT(SEQ ID NO 78)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fGdT*dT(SEQ ID NO 79)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fC2fU2fG2fA2fG2fG2fG(SEQ ID NO 81)；

wherein mA, mC, mG and mU are respectively 2' -O-methyl adenylic acid, cytidine, guanosine or uridine; 2fA, 2fC, 2fG and 2fU are 2' -fluoroadenosine, cytidine, guanosine or uridine, respectively; and is a phosphorothioate bond; and

the sense strand is at least substantially complementary to the antisense strand.

In another embodiment, (ii) the double stranded RNAi agent of the second dsRNA comprises a nucleotide sequence selected from the group consisting of (5'→ 3') seq id no:

UUUGAUAGCACCAAACCUAGAGCCCdTdT(SEQ ID NO:417)；

UUUGAUAGCACCAAACCUAGAGCCCdT*dT(SEQ ID NO:418)；

mUm[mUmGmAmUmAmGmCmAmCmCmAmAmAmCmCmUmAmGmAmGmCmCmC

dT*dT(SEQ ID NO:419)；

mUmUmUmGmAmUmAmGmCmAmCmCmAmAmAmCmCmUmAmGmAmGmCmCmC(SEQ ID NO:421)；

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fCmC2fUmA2fGmA2fGmC2fCmCdT*dT](SEQ ID NO:424)；

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fCmC2fUmA2fGmA2fGmC2fCmC(SEQ ID NO:425)；

mU2fAmU2fCmA2fAmA2fCmC2fUmC2fGmA2fUmA2fGmC2fAmA2fCmA2fCmC2fGmC(SEQ ID NO:429)；

mU2fU2fU2fG2fA2fU2fA2fG2fC2fA2fC2fC2fA2fA2fA2fC2fC2fU2fA2fG2fA2fG2fC2fC2fCdT*dT(SEQ ID NO:430)；

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fCmC2fUmA2fGmA2fGmC2fCmCdT*dT(SEQ ID NO:432)；

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fCmC2fUmA2fGmA2fGmC (SEQ ID NO: 433); and

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fC2fC2fU2fA2fG2fA2fG2fC(SEQ ID NO:434)

wherein mA, mC, mG and mU are respectively 2' -O-methyl adenylic acid, cytidine, guanosine or uridine; 2fA, 2fC, 2fG and 2fU are 2' -fluoroadenosine, cytidine, guanosine or uridine, respectively; and is a phosphorothioate bond; and

The sense strand is at least substantially complementary to the antisense strand.

In other embodiments, (ii) the double stranded RNAi agent antisense strand of the second dsRNA comprises a nucleotide sequence selected from the group consisting of (5'→ 3') seq id no:

UUUGCAAUGACUCUCCUAUCAGUCCdTdT(SEQ ID NO:448)；

UUUGCAAUGACUCUCCUAUCAGUCCdT*dT(SEQ ID NO:449)；

mUmUmUmGmCmAmAmUmGmAmCmUmCmUmCmCmUmAmUmCmAmGmUmCmCdT*dT(SEQ ID NO:450)；

mUmUmUmGmCmAmAmUmGmAmCmUmCmUmCmCmUmAmUmCmAmGmUmCmC(SEQ ID NO:452)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU2fCmCdT*dT(SEQ ID NO:455)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU2fCmC(SEQ ID NO:456)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fCmU2fC

mC(SEQ ID NO:458)；

2fUmU2fUmG2fCmA2fAmU2fGmA2fCmU2fCmU2fCmC2fUmA2fUmC2fAmG2fUmC2fCdT*dT(SEQ ID NO:459)；

mU2fAmU2fCmC2fUmA2fAmG2fUmC2fAmC2fAmC2fGmU2fUmU2fGmA2fCmU2fGmC(SEQ ID NO:460)；

mU2fU2fU2fG2fC2fA2fA2fU2fG2fA2fC2fU2fC2fU2fC2fC2fU2fA2fU2fC2fA2fG2fU2fC2fCdT*dT(SEQ ID NO:461)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU2fCmCdT*dT(SEQ ID NO:463)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU(SEQ ID NO:464)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fC2fU2fA2fU2fC2fA2fG2fU(SEQ ID NO:465)

wherein mA, mC, mG and mU are respectively 2' -O-methyl adenylic acid, cytidine, guanosine or uridine; 2fA, 2fC, 2fG and 2fU are 2' -fluoroadenosine, cytidine, guanosine or uridine, respectively; and is a phosphorothioate bond; and

the sense strand is at least substantially complementary to the antisense strand.

For example, when the RNAi agent comprises (iii): (i) in combination of the first dsRNA and (ii) the second dsRNA, (i) the antisense strand of the first dsRNA is selected from the group consisting of:

CAGUUGCGCAGUUUCUUGUCAGUUCdTdT(SEQ ID NO:17)；

CAGUUGCGCAGUUUCUUGUCAGUUCdT*dT(SEQ ID NO 18)；

AAGAGCUGAGGUCUCUGAGGGGdTdT (SEQ ID NO 64); and

aagagcucaggucugagggdt dT (SEQ ID NO 65); and

(ii) the antisense strand of the second dsRNA is selected from:

UUUGAUAGCACCAAACCUAGAGCCCdTdT(SEQ ID NO:417)；

UUUGAUAGCACCAAACCUAGAGCCCdT*dT(SEQ ID NO:418)；

UUGCAAUGACUCUCCUAUCAGUCCdT (SEQ ID NO: 448); and

UUUGCAAUGACUCUCCUAUCAGUCCdT*dT(SEQ ID NO:449)；

wherein is a phosphorothioate bond; and

the sense strand is at least substantially complementary to the antisense strand.

In one embodiment, (i) the first dsRNA has a double-helical structure of (SEQ ID NOS: 17 and 110) or (SEQ ID NOS: 18 and 111). In another, (ii) the second dsRNA has a double-helical structure (SEQ ID NOS: 417 and 808) or (SEQ ID NOS: 448 and 822).

Another embodiment provides an isolated cell comprising the double stranded RNAi agent of (i), (ii), or (iii).

For example, (i) the sense strand of the first dsRNA is no more than 30 nucleotides in length, and (i) the antisense strand of the first dsRNA is no more than 30 nucleotides in length. For example, (ii) the sense strand of the second dsRNA is no more than 30 nucleotides in length, and the antisense strand is no more than 30 nucleotides in length.

Another embodiment provides a pharmaceutical composition for inhibiting the expression of the CD320 gene, comprising the double stranded RNAi agent (i) or (iii). In addition, the pharmaceutical composition may comprise excipients.

Another embodiment provides a pharmaceutical composition for inhibiting expression of the LRP2 gene, the composition comprising a double stranded RNAi agent (ii) or (iii). In addition, the pharmaceutical composition may comprise excipients.

Another embodiment of the present invention provides a method for inhibiting the proliferation of Cancer Cells (CCs), comprising contacting the CCs with an inhibitor of CD320 and/or LRP2 in an amount effective to inhibit CC proliferation. For example, the CC may express CD320 and/or LRP2 or both.

Another embodiment of the invention provides a method of treating a treatment-resistant cancer in a subject who has previously received therapy comprising administering to the subject an inhibitor of CD320 and/or LRP2 in an amount effective to inhibit or kill Cancer Cells (CCs) present in the treatment-resistant cancer.

Another embodiment of the invention provides a method for treating cancer in a subject with recurrent or recurrent cancer, comprising administering to the subject an amount of an inhibitor of CD320 and/or LRP2 effective to inhibit or kill CC in the cancer.

CC is from a cancer selected from: melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular carcinoma, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

The CD320 inhibitor is selected from the group consisting of an antibody that binds CD320, a small molecule inhibitor of CD320, and an RNAi agent that hybridizes to a nucleic acid sequence encoding CD 320.

In addition, methods of inhibiting CC proliferation, treating a therapeutically-resistant cancer in a subject with recurrent or relapsed cancer, comprising administering a cancer therapeutic in combination with an RNAi agent that hybridizes to mRNA encoding CD320 or an RNAi agent that hybridizes to mRNA encoding LRP 2. For example, the cancer therapeutic is selected from an antifolate, an epigenetic regulator, or a small molecule or protein inhibitor of CD320 function or LRP2 function, such as an antibody to CD320 or an antibody to LRP 2. In addition, the method further comprises administering metformin. For example, RNAi agents include the antisense strands of table 5 or table 6.

The inhibitor is selected from an antibody that binds LRP2, a small molecule inhibitor of LRP2, and an RNAi agent that hybridizes to a nucleic acid sequence encoding LRP 2. For example, the methods further comprise administering a cancer therapeutic selected from the group consisting of: antifolates, epigenetic modulators or small molecule or protein inhibitors of LRP2 function, such as antibodies.

The methods further comprise administering a cancer therapeutic in combination with an RNAi agent that hybridizes to mRNA encoding LRP 2.

One embodiment of the present invention provides a method for inhibiting the proliferation of Cancer Cells (CC), comprising contacting the CC with a composition comprising an inhibitor of CD320 and an inhibitor of LRP2 in amounts effective to inhibit the proliferation of the CC. For example, the composition is a mixture comprising: i) a CD320 inhibitor selected from the group consisting of an antibody that binds CD320, a small molecule inhibitor of CD320, and an RNAi agent that hybridizes to a nucleic acid sequence encoding CD320, and any combination thereof, and ii) an LRP2 inhibitor selected from the group consisting of an antibody that binds LRP2, a small molecule inhibitor of LRP2, and an RNAi agent that hybridizes to a nucleic acid sequence encoding LRP2, and any combination thereof. In addition, the method further comprises administering a cancer therapeutic selected from the group consisting of: antifolates and epigenetic regulators. For example, an RNAi agent that hybridizes to an mRNA encoding CD320 comprises a first double-stranded ribonucleic acid (dsRNA) for inhibiting expression of CD320, wherein the first dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to a CD320 RNA transcript, and an RNAi agent that hybridizes to an mRNA encoding LRP2 comprises a second dsRNA for inhibiting expression of LRP2, wherein the second dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to an LRP2 RNA transcript. In another example, the antisense strand complementary to a CD320 RNA transcript is selected from table 5 and the antisense strand complementary to an RNA transcript of LRP2 is selected from table 6. The method further comprises administering a cancer therapeutic selected from the group consisting of: antifolates and epigenetic regulators. The method further comprises administering a cancer therapeutic selected from the immunomodulatory classes. In addition, the method further comprises administering metformin.

An aspect of one embodiment of the invention provides methods for inhibiting the expression of CD320 and LRP2 proteins such that the levels of these proteins are reduced in treated cells compared to their endogenous levels in untreated cells; this inhibition may also be referred to as knock-down of CD320 and LRP2 expression. The method requires the use of small interfering RNA molecules, otherwise called mixtures of sirnas, which direct mRNA sequences encoding CD320 or LRP2 to an enzymatic complex that leads to targeted disruption of these mrnas.

Another aspect of the invention provides methods for inhibiting the expression of LRP2 and CD320 proteins, alone or in combination, that inhibit the growth of a variety of cancer cells as compared to non-cancer (normal) cells. In some cases, knock-down of CD320 or LRP2 protein alone is sufficient to severely inhibit cancer cell proliferation compared to normal cells.

Another aspect of the invention provides for the inhibition of cancer cell proliferation by inhibiting the expression of the LRP2 receptor.

The mechanistic study of selectivity of porphyrin uptake by cancer cells has led to the generation of several unobvious compounds and methods of using the same. It has been found that knock-down of the expression of the CD320 gene or the LRP2 gene or simultaneous knock-down of the expression of the CD320 gene and the LRP2 gene in a group of lung cancer cell lines results in cell death or cell growth inhibition compared to normal fibroblasts. Fig. 1 shows an experimental summary. In these experiments, cells were plated on day 0. The following day (day 1), viral particles encoding short hairpin rna (shRNA) or unrelated shRNA controls against the CD320 gene and the LRP2 gene were added to the cell culture along with the reagent protamine sulfate that facilitates cellular entry of the viral particles.

Further studies showed that the knock down of the expression of the CD320 gene or LRP2 gene or the simultaneous knock down of the expression of the CD320 and LRP2 genes using small interfering rna (sirna) resulted in cell death or inhibition of cell growth in a panel of cancer cell lines (including lung cancer, prostate cancer, breast cancer, glioblastoma and melanoma) compared to normal fibroblasts (fig. 9-10). It was also found that in some cancer cell lines the knockdown of one gene, CD320 or LRP2, resulted in an increased expression of the other.

One aspect of the invention provides for the in vivo and in vitro knock-down of a CD320 receptor, a LRP2 receptor, or both, of a cancer cell expressing CD320 mRNA and/or LRP2 mRNA.

Another aspect of the invention is a method of inhibiting cell growth or causing cell death of a cancer cell treated with a compound as described herein, while leaving normal cells unaffected or with a lesser degree of inhibition of cell growth or producing less cell death compared to a cancer cell treated with the same amount of the compound.

Another aspect of the first compounds and methods of use is in selective therapies that inhibit cancer cell proliferation and/or kill cancer cells, while sparing normal cells, through inhibition of the LRP2 receptor.

Another aspect of the second compounds and methods of use is a selective therapy that inhibits cancer cell proliferation and/or kills cancer cells by inhibition of the CD320 receptor while sparing normal cells.

Another aspect of the invention provides cancer treatments for selectively inhibiting cancer cell proliferation and/or killing cancer cells by administering a therapy using one or more of the following: a first compound that is an inhibitor of the CD320 receptor, a second compound that is an inhibitor of the LRP2 receptor, or a combination thereof.

Drawings

The accompanying drawings, which are incorporated in and form a part of the specification, illustrate one or more embodiments of the present invention and, together with the description, serve to explain the principles of the invention. The drawings are only for the purpose of illustrating one or more embodiments of the invention and are not to be construed as limiting the invention. In the drawings:

figure 1 shows the experimental design of knockdown of CD320 and LRP2 in cells. On day 0, cells were plated. The following day (day 1), viral particles encoding short hairpin rna (shRNA) or non-targeted shRNA controls against CD320 and LRP2 mRNA were added to the cell culture along with the reagent protamine sulfate that facilitates cellular entry of the viral particles. Table 1 shows the sequences used. Each shRNA coding sequence is also combined with a unique drug resistance gene, which will enable selection of those cells that have taken up the shRNA; cells that did not take up shRNA did not survive. On day 2, drug selection was started. On day 3, cells were harvested and plated in new dishes. Only cells with the drug resistance gene, i.e. cells that have taken up shRNA virions, will survive this replating procedure. From day 4 onwards, the growth of each cultured cell was closely observed. Cells infected with the non-targeted negative control shRNA continued to grow-data not shown. The results for cell lines expressing CD320+ LRP2shRNA are shown in table 1.

FIGS. 2A-C show the sensitivity of cancer cell lines to knockdown of CD320 and LRP 2. Normal cells (GM05659 fibroblasts) or cancer cells were infected with lentiviruses expressing either the control sequence or shRNA of shCD320 and shLRP2, as shown in fig. 1. Cells were grown as depicted in FIG. 1. At day 9 post-lentivirus transfection, photographs of the cells were taken. The solid oval represents healthy growth of normal fibroblasts infected with shRNA against CD320 and LRP 2. The dashed ovals represent unhealthy dying cancer cells infected with shRNA targeting CD320 and LRP2 (fig. 2A). The fields of cells in fig. 2A were counted and quantified and are shown in fig. 2B. The data in fig. 2B was normalized to the control cell number and is shown in fig. 2C. Figure 2C shows that cell cultures of lentiviruses infected with shRNA encoding CD320 and LRP2 (white bars) contained far fewer cells than cell cultures exposed to shRNA control (black bars).

FIGS. 3A-F show protein level maps resulting from transfection of HEK293, MDA-MB-435S and MDA-MB-231 cells with siRNAs against LRP2 and CD 320. HEK293, MDA-MB-435S and MDA-MB-231 cells were transfected with siRNA as indicated at 20nM and incubated for 48 hours. Sirnas targeting CD320 are denoted OSC17 and OSC 47. Sirnas targeting LRP2 were denoted OSL245, OSL47, OSL104, OSL90, and OSL 119. Whole cell lysates were prepared and immunoblotted for CD320 and LRP2 protein levels. Protein levels were normalized to housekeeping control genes that were not affected by siRNA transfection. Figures 3A-F show fold change in protein levels compared to siscrambles (OSS1 or OSS 2). (mean +/-SEM, n ═ 3 is shown).

FIGS. 4A-F show cell maps after transfection of LnCAP, MCF-7 and U251 cells with siRNAs against LRP2 and CD 320. LnCAP, MCF-7 and U251 cells were transfected with siRNA indicated at 20nM and incubated for 48 hours. Sirnas targeting CD320 are denoted OSC17 and OSC 47. Sirnas targeting LRP2 were denoted OSL245, OSL47, OSL104, OSL90, and OSL 119. Whole cell lysates were prepared and immunoblotted for CD320 and LRP2 protein levels. Protein levels were normalized to housekeeping control genes that were not affected by siRNA transfection. FIGS. 4A-F show fold change in protein levels compared to siScramble (OSS 2).

Fig. 5A-C show protein level graphs after transfection of a172, DU145 and GM05659 cells with sirnas against LRP2 and CD 320. A172, DU145 and GM05659 cells were transfected with siRNA indicated at 20nM and incubated for 48 hours. Sirnas targeting CD320 are denoted OSC17 and OSC 47. Sirnas targeting LRP2 were denoted OSL245, OSL47, OSL104, OSL90, and OSL 119. Whole cell lysates were prepared and CD320 was immunoblotted. Protein levels were normalized to housekeeping control genes that were not affected by siRNA transfection. Fig. 5A-C show fold changes in protein levels compared to siScramble (OSS 2).

Figure 6 shows relative LRP2 protein expression profiles in various cell lines — lysates were made from the cell lines indicated on the x-axis and immunoblots were performed to determine LRP2 protein levels. Results represent the mean +/-SEM of 3 independent lysates.

FIGS. 7A-B show graphs of the effect of doxorubicin treatment on cell viability as measured by the CTG assay. A172 and HCC15 cells were plated at 1200 cells/well in 96-well plates. The following day, cells were treated with doxorubicin at the indicated concentrations. The viability of the cells was determined using the CTG assay 4 days after starting doxorubicin treatment. Dashed line representation calculation IC₅₀Negation of data of valueAnd (6) linear fitting.

Figure 8 is a schematic of a functional assay used to screen for the effect of siRNA on cell proliferation to facilitate quantification of the effect of knockdown of CD320 and LRP2 on cell proliferation. Cells were plated in 24-well plates. The next day, cells were transfected with sirnas targeting CD320(OSC17, OSC47) and/or LRP2(OSL231, OSL245) or control sirnas (OSS 2). For effective toxicity, cell lines may require repeated transfections and/or times (cell line dependent). In this experimental design, there is room for re-infection and some cell lines are required for effective toxicity. In addition, in a small subset of wells, cells were treated with doxorubicin alone as a positive control for toxicity. At the end of the study, cell growth of the cell lines was analyzed by CTG assay.

Figures 9A-E show graphs of the percent cell survival for cell proliferation for siCD320 and sirrp 2 — representative cell lines or normal fibroblasts of several cancer types (lung, brain) were transfected with sirnas targeting CD320(OSC17, OSC47) or LRP2 (OSL231, OSL245) alone or in combination or with negative control sirnas (OSS2) (20nM), as indicated, at 20nM alone or in combination (10 nM each). For effective toxicity, cells were repeatedly transfected and then viability was determined by CTG assay, as listed in table 9. In our assay, doxorubicin-treated cells were used as a positive control for cytotoxicity (table 8).

Fig. 10A-E show graphs of the effect of siCD320 and slrp 2 on cell proliferation-as indicated, representative cell lines of several cancer types (breast, prostate, skin) were transfected with sirnas targeting CD320(OSC17, OSC47) or LRP2 (OSL231, OSL245), alone or in combination. For effective toxicity, cells were repeatedly transfected and then viability was determined by CTG assay, as listed in table 9. In our assay, doxorubicin-treated cells were used as a positive control for cytotoxicity (table 8).

Figures 11A-B show the effect of siCD320 and sirrp 2 molar ratios on cell proliferation by different molar ratios of siRNA targeting CD320 and siRNA targeting LRP 2. As indicated, representative cell lines of both cancer types (breast, prostate) were transfected with different ratios of siRNA targeting CD320(OSC 17) or siRNA targeting LRP2 (OSL245) (0-20nM) or with negative control siRNA (OSS 2). For effective toxicity, cells were repeatedly transfected and then viability was determined by CTG assay. In our assay, doxorubicin-treated cells were used as a positive control for cytotoxicity (table 8).

FIGS. 12A-B show the duration of knockdown of siCD320 and siLRP2 on MDA-MD-231 cells. On day 0, a representative breast cancer cell line (MDA-MD-231) was transfected with 20nM siRNA targeting CD320(OSC17) or siRNA targeting LRP2 (OSL245) or negative control siRNA (OSS2), and the percentage of protein knockdown was analyzed by immunoblotting every day over a 5-day period. Protein levels were normalized to the negative control (OSS 2).

FIG. 13 is a schematic of complexation of Polyethyleneimine (PEI) and siRNA. PEI and siRNA were mixed together. Subsequently, polyplexes (nanoparticles, broadly) in the form of PEI-siRNA complexes were able to enter the cells.

FIG. 14 is a diagram showing siRNA as short RNA duplexes of typically 16 to 30 nucleotides; schematic representation of the siRNA leader sequence being complementary to mRNA expressed in the cell. Exogenous siRNA duplexes are introduced into cells by transfection. The siRNA duplexes are separated by the RISC/AGO (RNA-induced silencing complex) complex, whereby the guide strand of the siRNA hybridizes to its complementary mRNA molecule. mRNA is degraded by RISC/AGO complex having RNase activity, which results in mRNA degradation, and no protein encoded by the mRNA is produced. This results in a "knock-down" effect or reduced protein levels of the gene targeted by the siRNA compared to control-treated cells.

FIGS. 15A-B show graphs of A172 cell line or MDA-MD-435S cell line treated with control siRNA (OSS1, OSS2) and siRNA against CD320 mRNA (OSC17, OSC47) and LRP2 mRNA (OSL231, OSL245) to determine the effectiveness of INTERFERIN, a polyethanolamine transfection reagent in delivering siRNA into cancer cells.

FIGS. 16A-D show plated cells showing the effect of siCD320 and siLRP2 on 4 cell lines. As indicated, representative cell lines of 4 cancer types (breast, two prostate, skin) were transfected with siRNA targeting CD320 (OSC17) or siRNA targeting LRP2 (OSL245) at 20nM alone or in combination (10 nM each) or with negative control siRNA (OSS2) (20 nM). Cells were repeatedly transfected for effective toxicity as in table 9, and then analyzed by microscopy as indicated.

FIG. 17 shows a graphical representation of CD320 mRNA. UTR denotes untranslated regions and CDS denotes protein coding sequences.

Figure 18 shows a graphical display of LRP2 mRNA. UTR denotes untranslated regions and CDS denotes protein coding sequences.

FIGS. 19A-G show the structure of non-natural nucleotides that can be introduced into RNAi sequences. "B" represents a natural (G, C, A, U) RNA nucleobase, a DNA nucleobase or a non-natural nucleobase. FIG. 19A shows certain chemical modifications to the 2' -position of ribose and the phosphate moiety. FIGS. 19B-D show backbone modifications to ribose moieties containing bridging groups. FIG. 19E shows the deletion of the C2'-C3' linkage. FIGS. 19F-G show additional backbone modifications to the ribose moiety, in which a six-membered ring replaces the five-membered ring.

Figure 20 shows a schematic of an in vivo murine xenograft model of breast cancer. MDA-MB-231 cells were implanted into the flank of NSG mice and grown to a volume of 70mm³Then, CD 320-targeted siRNA (OSC17) and LRP 2-targeted siRNA (OSL245) were intratumorally injected every 4 days.

Detailed Description

One or more embodiments of the invention provide methods and RNAi compounds that modulate the expression of the CD320 gene and/or the LRP2 gene in a cell. In certain embodiments, the expression of the CD320 gene and/or LRP2 gene is reduced or inhibited using CD320 and/or LRP2 specific RNAi. Such inhibition may be useful in treating disorders, such as cancer, and/or in generating cell lines useful for screening for drugs to treat cancer.

The invention also relates to a method for (partial or complete) knockdown of a target gene.

One embodiment of a method of producing knockdown cells and organisms comprises introducing into a cell or organism in which a gene (referred to as a target gene) is to be knocked down a siRNA targeting about 16 to about 30 nucleotides (nt) of the gene and maintaining the produced cell or organism under conditions in which RNAi occurs, thereby causing degradation of the mRNA of the target gene, thereby producing the knocked down cell or organism. The knockdown cells and organisms produced by the methods of the invention are also the subject of embodiments of the invention.

Embodiments of the invention also relate to methods of examining or evaluating the function of a gene in a cell or organism. In one embodiment, about 16 to about 30nt of RNA targeted to mRNA of a gene for degradation is introduced into a cell or organism in which RNAi occurs. The cell or organism is referred to as a test cell or organism. The cell or organism is referred to as a test cell organism. The test cell or organism is maintained under conditions in which degradation of the mRNA of the gene occurs. The phenotype of the test cell or organism is then observed and compared to the phenotype of an appropriate control cell or organism, such as a corresponding cell or organism treated in the same manner except that the gene is not targeted. Instead of introducing siRNA into a test cell or organism, 16 to 30nt RNA that does not target mRNA for degradation may be introduced into a control cell or organism, although it is not necessary to do so. The difference between the phenotype of the test and control cells or organisms provides information about the function of the degraded mRNA.

RNA of about 16 to about 30 nucleotides is isolated or synthesized and then introduced into a cell or organism (test cell or test organism) in which RNAi occurs. The test cell or test organism is maintained under conditions in which degradation of the mRNA occurs. The phenotype of the test cell or organism is then observed and compared to the phenotype of a corresponding cell or organism treated in the same manner as the test cell or organism, with the appropriate controls, e.g., except that the target gene is not targeted. The difference between the phenotypes of the test and control cells or organisms provides information about the function of the target gene. The information provided may be sufficient to identify (define) the function of the gene or may be used in conjunction with information from other assays or analyses that do so.

Embodiments of the invention also encompass methods of treating a disease or condition associated with the presence of a protein in an individual comprising administering to the individual an RNA of about 16 to about 30 nucleotides that targets the mRNA of the protein (the mRNA encoding the protein) for degradation. Thus, no protein is produced, or to the extent that no treatment is present.

FIG. 14 shows that siRNA is a short RNA duplex of typically 16 to 30 nucleotides; the sequence of the siRNA is complementary to mRNA expressed in the cell. Exogenous siRNA duplexes are introduced into cells by transfection. The siRNA duplex is unwound by the RNA-induced silencing complex (RISC) such that the guide strand of the siRNA hybridizes to its complementary mRNA molecule. mRNA is degraded by the RISC/AGO complex, and has an RNase cleavage activity. The end result is degradation of the mRNA targeted by the siRNA and no production of the protein encoded by the mRNA. This results in a "knock-down" effect or reduced protein levels of the gene targeted by the siRNA compared to control-treated cells.

In one embodiment, at least one strand of the RNA molecule has a 3' overhang of about 1 to about 6 nucleotides in length (e.g., pyrimidine nucleotides, purine nucleotides). In other embodiments, the 3' overhang is about 1 to about 5 nucleotides, about 1 to about 3 nucleotides and about 2 to about 4 nucleotides in length, or, for example, if the guide strand is a 27-mer, the overhang can be up to 14 nucleotides. In one embodiment, the RNA molecule is double-stranded, one strand having a 3' overhang and the other strand may be a sticky end or have an overhang. In embodiments where the RNA molecule is double-stranded and both strands comprise an overhang, the length of the overhang may be the same or different for each strand. In a specific embodiment, the RNA of the invention comprises a strand of 21-27 nucleotides, which is watson-crick paired and has overhangs of about 1 to about 3, specifically about 2 nucleotides at both 3' ends of the RNA. To further improve the stability of the RNA of the invention, the 3' overhang may be stabilized against degradation. In one embodiment, the RNA is stabilized by including purine nucleotides, such as adenosine or guanosine nucleotides. Alternatively, substitution of pyrimidine nucleotides by non-natural nucleotides, for example, substitution of the 3 'overhang of uridine 2 nucleotide by 2' -deoxythymidine, is tolerated and does not affect the efficiency of RNAi. The absence of the 2' hydroxyl group significantly improves nuclease resistance of the overhang in tissue culture medium. The 3' -overhang can be further stabilized by the introduction of phosphorothioate groups instead of phosphodiesters.

The 16-30nt RNA molecules of the invention can be obtained using several techniques known to those skilled in the art. For example, RNA can be chemically synthesized or recombinantly produced using methods known in the art.

In order that the invention may be more readily understood, certain terms are first defined. In addition, it should be noted that whenever a value or range of values for a parameter is recited, values intermediate to the recited range of values and values are also intended to be part of the present invention.

The articles "a" and "an" are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. For example, "an element" means one element or more than one element, e.g., a plurality of elements.

The term "comprising" is used herein to mean, and is used interchangeably with, the phrase "including (but not limited to)".

The term "or" is used herein to mean, and is used interchangeably with, the term "and/or" unless the context clearly indicates otherwise.

As used herein, "CD 320" refers to a gene or protein. CD320 is also known as 8D6 antigen, CD320 antigen, 8D6A, cobalt amine transporter receptor, FDC-SM-8D6, FDC-signaling molecule 8D6, 8D6, TCBLR, TCblR, TCN 2R. The term CD320 includes human CD320, the amino acid and nucleotide sequences of which are found, for example, in Genbank accession nos. NM _016579.4 and NM _ 001165895.2; mouse CD320, the amino acid and nucleotide sequence of which can be found, for example, in Genbank accession No. nm — 019421.3; rat CD320, the amino acid and nucleotide sequence of which is found, for example, in Genbank accession No. nm — 001014201.1. Other examples of CD320 mRNA sequences are readily available using, for example, GenBank. Other information is seen in fig. 17.

The sequence of CD320 mRNA from Homo sapiens (Homo sapiens) is shown below: (> NM-016579.4 Homo sapiens) CD320 molecule (CD320), transcript variant 1, DNA

GTGCGCGTGCGCAGGGATAAGAGAGCGGTCTGGACAGCGCGTGGCCGGCGCCGCTGTGGGGACAGCATGA

GCGGCGGTTGGATGGCGCAGGTTGGAGCGTGGCGAACAGGGGCTCTGGGCCTGGCGCTGCTGCTGCTGCT

CGGCCTCGGACTAGGCCTGGAGGCCGCCGCGAGCCCGCTTTCCACCCCGACCTCTGCCCAGGCCGCAGGC

CCCAGCTCAGGCTCGTGCCCACCCACCAAGTTCCAGTGCCGCACCAGTGGCTTATGCGTGCCCCTCACCT

GGCGCTGCGACAGGGACTTGGACTGCAGCGATGGCAGCGATGAGGAGGAGTGCAGGATTGAGCCATGTAC

CCAGAAAGGGCAATGCCCACCGCCCCCTGGCCTCCCCTGCCCCTGCACCGGCGTCAGTGACTGCTCTGGG

GGAACTGACAAGAAACTGCGCAACTGCAGCCGCCTGGCCTGCCTAGCAGGCGAGCTCCGTTGCACGCTGA

GCGATGACTGCATTCCACTCACGTGGCGCTGCGACGGCCACCCAGACTGTCCCGACTCCAGCGACGAGCT

CGGCTGTGGAACCAATGAGATCCTCCCGGAAGGGGATGCCACAACCATGGGGCCCCCTGTGACCCTGGAG

AGTGTCACCTCTCTCAGGAATGCCACAACCATGGGGCCCCCTGTGACCCTGGAGAGTGTCCCCTCTGTCG

GGAATGCCACATCCTCCTCTGCCGGAGACCAGTCTGGAAGCCCAACTGCCTATGGGGTTATTGCAGCTGC

TGCGGTGCTCAGTGCAAGCCTGGTCACCGCCACCCTCCTCCTTTTGTCCTGGCTCCGAGCCCAGGAGCGC

CTCCGCCCACTGGGGTTACTGGTGGCCATGAAGGAGTCCCTGCTGCTGTCAGAACAGAAGACCTCGCTGC

CCTGAGGACAAGCACTTGCCACCACCGTCACTCAGCCCTGGGCGTAGCCGGACAGGAGGAGAGCAGTGAT

GCGGATGGGTACCCGGGCACACCAGCCCTCAGAGACCTGAGCTCTTCTGGCCACGTGGAACCTCGAACCC

GAGCTCCTGCAGAAGTGGCCCTGGAGATTGAGGGTCCCTGGACACTCCCTATGGAGATCCGGGGAGCTAG

GATGGGGAACCTGCCACAGCCAGAACTGAGGGGCTGGCCCCAGGCAGCTCCCAGGGGGTAGAACGGCCCT

GTGCTTAAGACACTCCTGCTGCCCCGTCTGAGGGTGGCGATTAAAGTTGCTTCACATCCTCAAAAAAAAA

AAAAAAAAAAAAAAAAAAAAAAA(SEQ ID NO.935).

The protein sequence of CD320 from the mRNA sequence above is shown below: (> sp | Q9NPF0| CD320_ HUMAN CD320 antigen OS ═ Homo sapiens (Homo sapiens) OX ═ 9606 GN ═ CD320 PE ═ 1 SV ═ 1

MSGGWMAQVGAWRTGALGLALLLLLGLGLGLEAAASPLSTPTSAQAAGPSSGSCPPTKFQ

CRTSGLCVPLTWRCDRDLDCSDGSDEEECRIEPCTQKGQCPPPPGLPCPCTGVSDCSGGT

DKKLRNCSRLACLAGELRCTLSDDCIPLTWRCDGHPDCPDSSDELGCGTNEILPEGDATT

MGPPVTLESVTSLRNATTMGPPVTLESVPSVGNATSSSAGDQSGSPTAYGVIAAAAVLSA

SLVTATLLLLSWLRAQERLRPLGLLVAMKESLLLSEQKTSLP(SEQ ID NO.936)

The sequence of CD320 mRNA from Homo sapiens (Homo sapiens) is shown below: (> NM-001165895.2 Homo sapiens) CD320 molecule (CD320), transcript variant 2, DNA

GCGTGCGCGTGCGCAGGGATAAGAGAGCGGTCTGGACAGCGCGTGGCCGGCGCCGCTGTGGGGACAGCATGAGCGGCGGTTGGATGGCGCAGGTTGGAGCGTGGCGAACAGGGGCTCTGGGCCTGGCGCTGCTGCTGCTGCTCGGCCTCGGACTAGGCCTGGAGGCCGCCGCGAGCCCGCTTTCCACCCCGACCTCTGCCCAGGCCGCAGGGATTGAGCCATGTACCCAGAAAGGGCAATGCCCACCGCCCCCTGGCCTCCCCTGCCCCTGCACCGGCGTCAGTGACTGCTCTGGGGGAACTGACAAGAAACTGCGCAACTGCAGCCGCCTGGCCTGCCTAGCAGGCGAGCTCCGTTGCACGCTGAGCGATGACTGCATTCCACTCACGTGGCGCTGCGACGGCCACCCAGACTGTCCCGACTCCAGCGACGAGCTCGGCTGTGGAACCAATGAGATCCTCCCGGAAGGGGATGCCACAACCATGGGGCCCCCTGTGACCCTGGAGAGTGTCACCTCTCTCAGGAATGCCACAACCATGGGGCCCCCTGTGACCCTGGAGAGTGTCCCCTCTGTCGGGAATGCCACATCCTCCTCTGCCGGAGACCAGTCTGGAAGCCCAACTGCCTATGGGGTTATTGCAGCTGCTGCGGTGCTCAGTGCAAGCCTGGTCACCGCCACCCTCCTCCTTTTGTCCTGGCTCCGAGCCCAGGAGCGCCTCCGCCCACTGGGGTTACTGGTGGCCATGAAGGAGTCCCTGCTGCTGTCAGAACAGAAGACCTCGCTGCCCTGAGGACAAGCACTTGCCACCACCGTCACTCAGCCCTGGGCGTAGCCGGACAGGAGGAGAGCAGTGATGCGGATGGGTACCCGGGCACACCAGCCCTCAGAGACCTGAGCTCTTCTGGCCACGTGGAACCTCGAACCCGAGCTCCTGCAGAAGTGGCCCTGGAGATTGAGGGTCCCTGGACACTCCCTATGGAGATCCGGGGAGCTAGGATGGGGAACCTGCCACAGCCAGAACTGAGGGGCTGGCCCCAGGCAGCTCCCAGGGGGTAGAACGGCCCTGTGCTTAAGACACTCCTGCTGCCCCGTCTGAGGGTGGCAATTAAAGTTGCTTCACATCCTC(SEQ ID NO.937)

The protein sequence of CD320 from the mRNA sequence above is shown below: (> sp | Q9NPF0-2| CD320_ HUMAN CD320 antigen isoform 2 OS ═ Homo sapiens (Homo sapiens) OX ═ 9606 GN ═ CD320

MSGGWMAQVGAWRTGALGLALLLLLGLGLGLEAAASPLSTPTSAQAAGIEPCTQKGQCPPPPGLPCPCTGVSDCSGGTDKKLRNCSRLACLAGELRCTLSDDCIPLTWRCDGHPDCPDSSDELGCGTNEILPEGDATTMGPPVTLESVTSLRNATTMGPPVTLESVPSVGNATSSSAGDQSGSPTAYGVIAAAAVLSASLVTATLLLLSWLRAQERLRPLGLLVAMKESLLLSEQKTSLP(SEQ ID NO.938)

In addition, "LRP 2" as used herein refers to a gene or protein. LRP2 is also known as megalin, LRP-2, glycoprotein 330, DBS, GP330, calcium sensor protein, Heymann nephritis antigen homolog, low density lipoprotein receptor-associated protein 2, EC 1.1.2.3, EC 3.4.21.9, LDL receptor-associated protein 2. The term LRP2 includes human LRP2, the amino acid and nucleotide sequence of which can be found, for example, in Genbank accession No. nm — 004525.3; mouse LRP2, the amino acid and nucleotide sequence of which can be found, for example, in Genbank accession No. nm — 001081088.2; rat LRP2, the amino acid and nucleotide sequence of which can be found, for example, in Genbank accession No. nm — 030827.1. Other examples of mRNA sequences are readily available using, for example, GenBank, LRP 2. Other information is seen in fig. 18.

An example of LRP2 is: NM — 004525.3 Homo sapiens (Homo sapiens) LDL receptor associated protein 2(LRP2), DNA:

GGTCTAAAGGGCTTTATGCACTGTCTGGAGGGTGGGGACTGGCGCGGGTAGAAAACGGGATGCCTCGGGC

GTGGGGGCAGGCTTTTGGCCACTAGGAGCTGGCGGAGGTGCAGACCTAAAGGAGCGTTCGCTAGCAGAGG

CGCTGCCGGTGCGGTGTGCTACGCGCGCCCACCTCCCGGGGAAGGAACGGCGAGGCCGGGGACCGTCGCG

GAGATGGATCGCGGGCCGGCAGCAGTGGCGTGCACGCTGCTCCTGGCTCTCGTCGCCTGCCTAGCGCCGG

CCAGTGGCCAAGAATGTGACAGTGCGCATTTTCGCTGTGGAAGTGGGCATTGCATCCCTGCAGACTGGAG

GTGTGATGGGACCAAAGACTGTTCAGATGACGCGGATGAAATTGGCTGCGCTGTTGTGACCTGCCAGCAG

GGCTATTTCAAGTGCCAGAGTGAGGGACAATGCATCCCCAACTCCTGGGTGTGTGACCAAGATCAAGACT

GTGATGATGGCTCAGATGAACGTCAAGATTGCTCACAAAGTACATGCTCAAGTCATCAGATAACATGCTC

CAATGGTCAGTGTATCCCAAGTGAATACAGGTGCGACCACGTCAGAGACTGCCCCGATGGAGCTGATGAG

AATGACTGCCAGTACCCAACATGTGAGCAGCTTACTTGTGACAATGGGGCCTGCTATAACACCAGTCAGA

AGTGTGATTGGAAAGTTGATTGCAGGGACTCCTCAGATGAAATCAACTGCACTGAGATATGCTTGCACAA

TGAGTTTTCATGTGGCAATGGAGAGTGTATCCCTCGTGCTTATGTCTGTGACCATGACAATGATTGCCAA

GACGGCAGTGACGAACATGCTTGCAACTATCCGACCTGCGGTGGTTACCAGTTCACTTGCCCCAGTGGCC

GATGCATTTATCAAAACTGGGTTTGTGATGGAGAAGATGACTGTAAAGATAATGGAGATGAAGATGGATG

TGAAAGCGGTCCTCATGATGTTCATAAATGTTCCCCAAGAGAATGGTCTTGCCCAGAGTCGGGACGATGC

ATCTCCATTTATAAAGTTTGTGATGGGATTTTAGATTGCCCAGGAAGAGAAGATGAAAACAACACTAGTA

CCGGAAAATACTGTAGTATGACTCTGTGCTCTGCCTTGAACTGCCAGTACCAGTGCCATGAGACGCCGTA

TGGAGGAGCGTGTTTTTGTCCCCCAGGTTATATCATCAACCACAATGACAGCCGTACCTGTGTTGAGTTT

GATGATTGCCAGATATGGGGAATTTGTGACCAGAAGTGTGAAAGCCGACCTGGCCGTCACCTGTGCCACT

GTGAAGAAGGGTATATCTTGGAGCGTGGACAGTATTGCAAAGCTAATGATTCCTTTGGCGAGGCCTCCAT

TATCTTCTCCAATGGTCGGGATTTGTTAATTGGTGATATTCATGGAAGGAGCTTCCGGATCCTAGTGGAG

TCTCAGAATCGTGGAGTGGCCGTGGGTGTGGCTTTCCACTATCACCTGCAAAGAGTTTTTTGGACAGACA

CCGTGCAAAATAAGGTTTTTTCAGTTGACATTAATGGTTTAAATATCCAAGAGGTTCTCAATGTTTCTGT

TGAAACCCCAGAGAACCTGGCTGTGGACTGGGTTAATAATAAAATCTATCTAGTGGAAACCAAGGTCAAC

CGCATAGATATGGTAAATTTGGATGGAAGCTATCGGGTTACCCTTATAACTGAAAACTTGGGGCATCCTA

GAGGAATTGCCGTGGACCCAACTGTTGGTTATTTATTTTTCTCAGATTGGGAGAGCCTTTCTGGGGAACC

TAAGCTGGAAAGGGCATTCATGGATGGCAGCAACCGTAAAGACTTGGTGAAAACAAAGCTGGGATGGCCT

GCTGGGGTAACTCTGGATATGATATCGAAGCGTGTTTACTGGGTTGACTCTCGGTTTGATTACATTGAAA

CTGTAACTTATGATGGAATTCAAAGGAAGACTGTAGTTCATGGAGGCTCCCTCATTCCTCATCCCTTTGG

AGTAAGCTTATTTGAAGGTCAGGTGTTCTTTACAGATTGGACAAAGATGGCCGTGCTGAAGGCAAACAAG

TTCACAGAGACCAACCCACAAGTGTACTACCAGGCTTCCCTGAGGCCCTATGGAGTGACTGTTTACCATT

CCCTCAGACAGCCCTATGCTACCAATCCGTGTAAAGATAACAATGGGGGCTGTGAGCAGGTCTGTGTCCT

CAGCCACAGAACAGATAATGATGGTTTGGGTTTCCGTTGCAAGTGCACATTCGGCTTCCAACTGGATACA

GATGAGCGCCACTGCATTGCTGTTCAGAATTTCCTCATTTTTTCATCCCAAGTTGCTATTCGTGGGATCC

CGTTCACCTTGTCTACCCAGGAAGATGTCATGGTTCCAGTTTCGGGGAATCCTTCTTTCTTTGTCGGGAT

TGATTTTGACGCCCAGGACAGCACTATCTTTTTTTCAGATATGTCAAAACACATGATTTTTAAGCAAAAG

ATTGATGGCACAGGAAGAGAAATTCTCGCAGCTAACAGGGTGGAAAATGTTGAAAGTTTGGCTTTTGATT

GGATTTCAAAGAATCTCTATTGGACAGACTCTCATTACAAGAGTATCAGTGTCATGAGGCTAGCTGATAA

AACGAGACGCACAGTAGTTCAGTATTTAAATAACCCACGGTCGGTGGTAGTTCATCCTTTTGCCGGGTAT

CTATTCTTCACTGATTGGTTCCGTCCTGCTAAAATTATGAGAGCATGGAGTGACGGATCTCACCTCTTGC

CTGTAATAAACACTACTCTTGGATGGCCCAATGGCTTGGCCATCGATTGGGCTGCTTCACGATTGTACTG

GGTAGATGCCTATTTTGATAAAATTGAGCACAGCACCTTTGATGGTTTAGACAGAAGAAGACTGGGCCAT

ATAGAGCAGATGACACATCCGTTTGGACTTGCCATCTTTGGAGAGCATTTATTTTTTACTGACTGGAGAC

TGGGTGCCATTATTCGAGTCAGGAAAGCAGATGGTGGAGAAATGACAGTTATCCGAAGTGGCATTGCTTA

CATACTGCATTTGAAATCGTATGATGTCAACATCCAGACTGGTTCTAACGCCTGTAATCAACCCACGCAT

CCTAACGGTGACTGCAGCCACTTCTGCTTCCCGGTGCCAAATTTCCAGCGAGTGTGTGGGTGCCCTTATG

GAATGAGGCTGGCTTCCAATCACTTGACATGCGAGGGGGACCCAACCAATGAACCACCCACAGAGCAGTG

TGGCTTATTTTCCTTCCCCTGTAAAAATGGCAGATGTGTGCCCAATTACTATCTCTGTGATGGAGTCGAT

GATTGTCATGATAACAGTGATGAGCAACTATGTGGCACACTTAATAATACCTGTTCATCTTCGGCGTTCA

CCTGTGGCCATGGGGAGTGCATTCCTGCACACTGGCGCTGTGACAAACGCAACGACTGTGTGGATGGCAG

TGATGAGCACAACTGCCCCACCCACGCACCTGCTTCCTGCCTTGACACCCAATACACCTGTGATAATCAC

CAGTGTATCTCAAAGAACTGGGTCTGTGACACAGACAATGATTGTGGGGATGGATCTGATGAAAAGAACT

GCAATTCGACAGAGACATGCCAACCTAGTCAGTTTAATTGCCCCAATCATCGATGTATTGACCTATCGTT

TGTCTGTGATGGTGACAAGGATTGTGTTGATGGATCTGATGAGGTTGGTTGTGTATTAAACTGTACTGCT

TCTCAATTCAAGTGTGCCAGTGGGGATAAATGTATTGGCGTCACAAATCGTTGTGATGGTGTTTTTGATT

GCAGTGACAACTCGGATGAAGCAGGCTGTCCAACCAGGCCTCCTGGTATGTGCCACTCAGATGAATTTCA

GTGCCAAGAAGATGGTATCTGCATCCCGAACTTCTGGGAATGTGATGGGCATCCAGACTGCCTCTATGGA

TCTGATGAGCACAATGCCTGTGTCCCCAAGACTTGCCCTTCATCATATTTCCACTGTGACAACGGAAACT

GCATCCACAGGGCATGGCTCTGTGATCGGGACAATGACTGCGGGGATATGAGTGATGAGAAGGACTGCCC

TACTCAGCCCTTTCGCTGTCCTAGTTGGCAATGGCAGTGTCTTGGCCATAACATCTGTGTGAATCTGAGT

GTAGTGTGTGATGGCATCTTTGACTGCCCCAATGGGACAGATGAGTCCCCACTTTGCAATGGGAACAGCT

GCTCAGATTTCAATGGTGGTTGTACTCACGAGTGTGTTCAAGAGCCCTTTGGGGCTAAATGCCTATGTCC

ATTGGGATTCTTACTTGCCAATGATTCTAAGACCTGTGAAGACATAGATGAATGTGATATTCTAGGCTCT

TGTAGCCAGCACTGTTACAATATGAGAGGTTCTTTCCGGTGCTCGTGTGATACAGGCTACATGTTAGAAA

GTGATGGGAGGACTTGCAAAGTTACAGCATCTGAGAGTCTGCTGTTACTTGTGGCAAGTCAGAACAAAAT

TATTGCCGACAGTGTCACCTCCCAGGTCCACAATATCTATTCATTGGTCGAGAATGGTTCTTACATTGTA

GCTGTTGATTTTGATTCAATTAGTGGTCGTATCTTTTGGTCTGATGCAACTCAGGGTAAAACCTGGAGTG

CGTTTCAAAATGGAACGGACAGAAGAGTGGTATTTGACAGTAGCATCATCTTGACTGAAACTATTGCAAT

AGATTGGGTAGGTCGTAATCTTTACTGGACAGACTATGCTCTGGAAACAATTGAAGTCTCCAAAATTGAT

GGGAGCCACAGGACTGTGCTGATTAGTAAAAACCTAACAAATCCAAGAGGACTAGCATTAGATCCCAGAA

TGAATGAGCATCTACTGTTCTGGTCTGACTGGGGCCACCACCCTCGCATCGAGCGAGCCAGCATGGACGG

CAGCATGCGCACTGTCATTGTCCAGGACAAGATCTTCTGGCCCTGCGGCTTAACTATTGACTACCCCAAC

AGACTGCTCTACTTCATGGACTCCTATCTTGATTACATGGACTTTTGTGATTATAATGGACACCATCGGA

GACAGGTGATAGCCAGTGATTTGATTATACGGCACCCCTATGCCCTAACTCTCTTTGAAGACTCTGTGTA

CTGGACTGACCGTGCTACTCGTCGGGTTATGCGAGCCAACAAGTGGCATGGAGGGAACCAGTCAGTTGTA

ATGTATAATATTCAATGGCCCCTTGGGATTGTTGCGGTTCATCCTTCGAAACAACCAAATTCCGTGAATC

CATGTGCCTTTTCCCGCTGCAGCCATCTCTGCCTGCTTTCCTCACAGGGGCCTCATTTTTACTCCTGTGT

TTGTCCTTCAGGATGGAGTCTGTCTCCTGATCTCCTGAATTGCTTGAGAGATGATCAACCTTTCTTAATA

ACTGTAAGGCAACATATAATTTTTGGAATCTCCCTTAATCCTGAGGTGAAGAGCAATGATGCTATGGTCC

CCATAGCAGGGATACAGAATGGTTTAGATGTTGAATTTGATGATGCTGAGCAATACATCTATTGGGTTGA

AAATCCAGGTGAAATTCACAGAGTGAAGACAGATGGCACCAACAGGACAGTATTTGCTTCTATATCTATG

GTGGGGCCTTCTATGAACCTGGCCTTAGATTGGATTTCAAGAAACCTTTATTCTACCAATCCTAGAACTC

AGTCAATCGAGGTTTTGACACTCCACGGAGATATCAGATACAGAAAAACATTGATTGCCAATGATGGGAC

AGCTCTTGGAGTTGGCTTTCCAATTGGCATAACTGTTGATCCTGCTCGTGGGAAGCTGTACTGGTCAGAC

CAAGGAACTGACAGTGGGGTTCCTGCCAAGATCGCCAGTGCTAACATGGATGGCACATCTGTGAAAACTC

TCTTTACTGGGAACCTCGAACACCTGGAGTGTGTCACTCTTGACATCGAAGAGCAGAAACTCTACTGGGC

AGTCACTGGAAGAGGAGTGATTGAAAGAGGAAACGTGGATGGAACAGATCGAATGATCCTGGTACACCAG

CTTTCCCACCCCTGGGGAATTGCAGTCCATGATTCTTTCCTTTATTATACTGATGAACAGTATGAGGTCA

TTGAAAGAGTTGATAAGGCCACTGGGGCCAACAAAATAGTCTTGAGAGATAATGTTCCAAATCTGAGGGG

TCTTCAAGTTTATCACAGACGCAATGCCGCCGAATCCTCAAATGGCTGTAGCAACAACATGAATGCCTGT

CAGCAGATTTGCCTGCCTGTACCAGGAGGATTGTTTTCCTGCGCCTGTGCCACTGGATTTAAACTCAATC

CTGATAATCGGTCCTGCTCTCCATATAACTCTTTCATTGTTGTTTCAATGCTGTCTGCAATCAGAGGCTT

TAGCTTGGAATTGTCAGATCATTCAGAAACCATGGTGCCGGTGGCAGGCCAAGGACGAAACGCACTGCAT

GTGGATGTGGATGTGTCCTCTGGCTTTATTTATTGGTGTGATTTTAGCAGCTCAGTGGCATCTGATAATG

CGATCCGTAGAATTAAACCAGATGGATCTTCTCTGATGAACATTGTGACACATGGAATAGGAGAAAATGG

AGTCCGGGGTATTGCAGTGGATTGGGTAGCAGGAAATCTTTATTTCACCAATGCCTTTGTTTCTGAAACA

CTGATAGAAGTTCTGCGGATCAATACTACTTACCGCCGTGTTCTTCTTAAAGTCACAGTGGACATGCCTA

GGCATATTGTTGTAGATCCCAAGAACAGATACCTCTTCTGGGCTGACTATGGGCAGAGACCAAAGATTGA

GCGTTCTTTCCTTGACTGTACCAATCGAACAGTGCTTGTGTCAGAGGGCATTGTCACACCACGGGGCTTG

GCAGTGGACCGAAGTGATGGCTACGTTTATTGGGTTGATGATTCTTTAGATATAATTGCAAGGATTCGTA

TCAATGGAGAGAACTCTGAAGTGATTCGTTATGGCAGTCGTTACCCAACTCCTTATGGCATCACTGTTTT

TGAAAATTCTATCATATGGGTAGATAGGAATTTGAAAAAGATCTTCCAAGCCAGCAAGGAACCAGAGAAC

ACAGAGCCACCCACAGTGATAAGAGACAATATCAACTGGCTAAGAGATGTGACCATCTTTGACAAGCAAG

TCCAGCCCCGGTCACCAGCAGAGGTCAACAACAACCCTTGCTTGGAAAACAATGGTGGGTGCTCTCATCT

CTGCTTTGCTCTGCCTGGATTGCACACCCCAAAATGTGACTGTGCCTTTGGGACCCTGCAAAGTGATGGC

AAGAATTGTGCCATTTCAACAGAAAATTTCCTCATCTTTGCCTTGTCTAATTCCTTGAGAAGCTTACACT

TGGACCCTGAAAACCATAGCCCACCTTTCCAAACAATAAATGTGGAAAGAACTGTCATGTCTCTAGACTA

TGACAGTGTAAGTGATAGAATCTACTTCACACAAAATTTAGCCTCTGGAGTTGGACAGATTTCCTATGCC

ACCCTGTCTTCAGGGATCCATACTCCAACTGTCATTGCTTCAGGTATAGGGACTGCTGATGGCATTGCCT

TTGACTGGATTACTAGAAGAATTTATTACAGTGACTACCTCAACCAGATGATTAATTCCATGGCTGAAGA

TGGGTCTAACCGCACTGTGATAGCCCGCGTTCCAAAACCAAGAGCAATTGTGTTAGATCCCTGCCAAGGG

TACCTGTACTGGGCTGACTGGGATACACATGCCAAAATCGAGAGAGCCACATTGGGAGGAAACTTCCGCG

TACCCATTGTGAACAGCAGTCTGGTCATGCCCAGTGGGCTGACTCTGGACTATGAAGAGGACCTTCTCTA

CTGGGTGGATGCTAGTCTGCAGAGGATTGAACGCAGCACTCTGACGGGCGTGGATCGTGAAGTCATTGTC

AATGCAGCCGTTCATGCTTTTGGCTTGACTCTCTATGGCCAGTATATTTACTGGACTGACTTGTACACAC

AAAGAATTTACCGAGCTAACAAATATGACGGGTCAGGTCAGATTGCAATGACCACAAATTTGCTCTCCCA

GCCCAGGGGAATCAACACTGTTGTGAAGAACCAGAAACAACAGTGTAACAATCCTTGTGAACAGTTTAAT

GGGGGCTGCAGCCATATCTGTGCACCAGGTCCAAATGGTGCCGAGTGCCAGTGTCCACATGAGGGCAACT

GGTATTTGGCCAACAACAGGAAGCACTGCATTGTGGACAATGGTGAACGATGTGGTGCATCTTCCTTCAC

CTGCTCCAATGGGCGCTGCATCTCGGAAGAGTGGAAGTGTGATAATGACAACGACTGTGGGGATGGCAGT

GATGAGATGGAAAGTGTCTGTGCACTTCACACCTGCTCACCGACAGCCTTCACCTGTGCCAATGGGCGAT

GTGTCCAATACTCTTACCGCTGTGATTACTACAATGACTGTGGTGATGGCAGTGATGAGGCAGGGTGCCT

GTTCAGGGACTGCAATGCCACCACGGAGTTTATGTGCAATAACAGAAGGTGCATACCTCGTGAGTTTATC

TGCAATGGTGTAGACAACTGCCATGATAATAACACTTCAGATGAGAAAAATTGCCCTGATCGCACTTGCC

AGTCTGGATACACAAAATGTCATAATTCAAATATTTGTATTCCTCGCGTTTATTTGTGTGACGGAGACAA

TGACTGTGGAGATAACAGTGATGAAAACCCTACTTATTGCACCACTCACACGTGCAGCAGCAGTGAGTTC

CAATGCGCATCTGGGCGCTGTATTCCTCAACATTGGTATTGTGATCAAGAAACAGATTGTTTTGATGCCT

CTGATGAACCTGCCTCTTGTGGTCACTCTGAGCGAACATGCCTAGCTGATGAGTTCAAGTGTGATGGTGG

GAGGTGCATCCCAAGCGAATGGATCTGTGACGGTGATAATGACTGTGGGGATATGAGTGACGAGGATAAA

AGGCACCAGTGTCAGAATCAAAACTGCTCGGATTCCGAGTTTCTCTGTGTAAATGACAGACCTCCGGACA

GGAGGTGCATTCCCCAGTCTTGGGTCTGTGATGGCGATGTGGATTGTACTGACGGCTACGATGAGAATCA

GAATTGCACCAGGAGAACTTGCTCTGAAAATGAATTCACCTGTGGTTACGGACTGTGTATCCCAAAGATA

TTCAGGTGTGACCGGCACAATGACTGTGGTGACTATAGCGACGAGAGGGGCTGCTTATACCAGACTTGCC

AACAGAATCAGTTTACCTGTCAGAACGGGCGCTGCATTAGTAAAACCTTCGTCTGTGATGAGGATAATGA

CTGTGGAGACGGATCTGATGAGCTGATGCACCTGTGCCACACCCCAGAACCCACGTGTCCACCTCACGAG

TTCAAGTGTGACAATGGGCGCTGCATCGAGATGATGAAACTCTGCAACCACCTAGATGACTGTTTGGACA

ACAGCGATGAGAAAGGCTGTGGCATTAATGAATGCCATGACCCTTCAATCAGTGGCTGCGATCACAACTG

CACAGACACCTTAACCAGTTTCTATTGTTCCTGTCGTCCTGGTTACAAGCTCATGTCTGACAAGCGGACT

TGTGTTGATATTGATGAATGCACAGAGATGCCTTTTGTCTGTAGCCAGAAGTGTGAGAATGTAATAGGCT

CCTACATCTGTAAGTGTGCCCCAGGCTACCTCCGAGAACCAGATGGAAAGACCTGCCGGCAAAACAGTAA

CATCGAACCCTATCTCATTTTTAGCAACCGTTACTATTTGAGAAATTTAACTATAGATGGCTATTTTTAC

TCCCTCATCTTGGAAGGACTGGACAATGTTGTGGCATTAGATTTTGACCGAGTAGAGAAGAGATTGTATT

GGATTGATACACAGAGGCAAGTCATTGAGAGAATGTTTCTGAATAAGACAAACAAGGAGACAATCATAAA

CCACAGACTACCAGCTGCAGAAAGTCTGGCTGTAGACTGGGTTTCCAGAAAGCTCTACTGGTTGGATGCC

CGCCTGGATGGCCTCTTTGTCTCTGACCTCAATGGTGGACACCGCCGCATGCTGGCCCAGCACTGTGTGG

ATGCCAACAACACCTTCTGCTTTGATAATCCCAGAGGACTTGCCCTTCACCCTCAATATGGGTACCTCTA

CTGGGCAGACTGGGGTCACCGCGCATACATTGGGAGAGTAGGCATGGATGGAACCAACAAGTCTGTGATA

ATCTCCACCAAGTTAGAGTGGCCTAATGGCATCACCATTGATTACACCAATGATCTACTCTACTGGGCAG

ATGCCCACCTGGGTTACATAGAGTACTCTGATTTGGAGGGCCACCATCGACACACGGTGTATGATGGGGC

ACTGCCTCACCCTTTCGCTATTACCATTTTTGAAGACACTATTTATTGGACAGATTGGAATACAAGGACA

GTGGAAAAGGGAAACAAATATGATGGATCAAATAGACAGACACTGGTGAACACAACACACAGACCATTTG

ACATCCATGTGTACCATCCATATAGGCAGCCCATTGTGAGCAATCCCTGTGGTACCAACAATGGTGGCTG

TTCTCATCTCTGCCTCATCAAGCCAGGAGGAAAAGGGTTCACTTGCGAGTGTCCAGATGACTTCCGCACC

CTTCAGCTGAGTGGCAGCACCTACTGCATGCCCATGTGCTCCAGCACCCAGTTCCTGTGCGCTAACAATG

AAAAGTGCATTCCTATCTGGTGGAAATGTGATGGACAGAAAGACTGCTCAGATGGCTCTGATGAACTGGC

CCTTTGCCCGCAGCGCTTCTGCCGACTGGGACAGTTCCAGTGCAGTGACGGCAACTGCACCAGCCCGCAG

ACTTTATGCAATGCTCACCAAAATTGCCCTGATGGGTCTGATGAAGACCGTCTTCTTTGTGAGAATCACC

ACTGTGACTCCAATGAATGGCAGTGCGCCAACAAACGTTGCATCCCAGAATCCTGGCAGTGTGACACATT

TAACGACTGTGAGGATAACTCAGATGAAGACAGTTCCCACTGTGCCAGCAGGACCTGCCGGCCGGGCCAG

TTTCGGTGTGCTAATGGCCGCTGCATCCCGCAGGCCTGGAAGTGTGATGTGGATAATGATTGTGGAGACC

ACTCGGATGAGCCCATTGAAGAATGCATGAGCTCTGCCCATCTCTGTGACAACTTCACAGAATTCAGCTG

CAAAACAAATTACCGCTGCATCCCAAAGTGGGCCGTGTGCAATGGTGTAGATGACTGCAGGGACAACAGT

GATGAGCAAGGCTGTGAGGAGAGGACATGCCATCCTGTGGGGGATTTCCGCTGTAAAAATCACCACTGCA

TCCCTCTTCGTTGGCAGTGTGATGGGCAAAATGACTGTGGAGATAACTCAGATGAGGAAAACTGTGCTCC

CCGGGAGTGCACAGAGAGCGAGTTTCGATGTGTCAATCAGCAGTGCATTCCCTCGCGATGGATCTGTGAC

CATTACAACGACTGTGGGGACAACTCAGATGAACGGGACTGTGAGATGAGGACCTGCCATCCTGAATATT

TTCAGTGTACAAGTGGACATTGTGTACACAGTGAACTGAAATGCGATGGATCCGCTGACTGTTTGGATGC

GTCTGATGAAGCTGATTGTCCCACACGCTTTCCTGATGGTGCATACTGCCAGGCTACTATGTTCGAATGC

AAAAACCATGTTTGTATCCCGCCATATTGGAAATGTGATGGCGATGATGACTGTGGCGATGGTTCAGATG

AAGAACTTCACCTGTGCTTGGATGTTCCCTGTAATTCACCAAACCGTTTCCGGTGTGACAACAATCGCTG

CATTTATAGTCATGAGGTGTGCAATGGTGTGGATGACTGTGGAGATGGAACTGATGAGACAGAGGAGCAC

TGTAGAAAACCGACCCCTAAACCTTGTACAGAATATGAATATAAGTGTGGCAATGGGCATTGCATTCCAC

ATGACAATGTGTGTGATGATGCCGATGACTGTGGTGACTGGTCCGATGAACTGGGTTGCAATAAAGGAAA

AGAAAGAACATGTGCTGAAAATATATGCGAGCAAAATTGTACCCAATTAAATGAAGGAGGATTTATCTGC

TCCTGTACAGCTGGGTTCGAAACCAATGTTTTTGACAGAACCTCCTGTCTAGATATCAATGAATGTGAAC

AATTTGGGACTTGTCCCCAGCACTGCAGAAATACCAAAGGAAGTTATGAGTGTGTCTGTGCTGATGGCTT

CACGTCTATGAGTGACCGCCCTGGAAAACGATGTGCAGCTGAGGGTAGCTCTCCTTTGTTGCTACTGCCT

GACAATGTCCGAATTCGAAAATATAATCTCTCATCTGAGAGGTTCTCAGAGTATCTTCAAGATGAGGAAT

ATATCCAAGCTGTTGATTATGATTGGGATCCCAAGGACATAGGCCTCAGTGTTGTGTATTACACTGTGCG

AGGGGAGGGCTCTAGGTTTGGTGCTATCAAACGTGCCTACATCCCCAACTTTGAATCCGGCCGCAATAAT

CTTGTGCAGGAAGTTGACCTGAAACTGAAATACGTAATGCAGCCAGATGGAATAGCAGTGGACTGGGTTG

GAAGGCATATTTACTGGTCAGATGTCAAGAATAAACGCATTGAGGTGGCTAAACTTGATGGAAGGTACAG

AAAGTGGCTGATTTCCACTGACCTGGACCAACCAGCTGCTATTGCTGTGAATCCCAAACTAGGGCTTATG

TTCTGGACTGACTGGGGAAAGGAACCTAAAATCGAGTCTGCCTGGATGAATGGAGAGGACCGCAACATCC

TGGTTTTCGAGGACCTTGGTTGGCCAACTGGCCTTTCTATCGATTATTTGAACAATGACCGAATCTACTG

GAGTGACTTCAAGGAGGACGTTATTGAAACCATAAAATATGATGGGACTGATAGGAGAGTCATTGCAAAG

GAAGCAATGAACCCTTACAGCCTGGACATCTTTGAAGACCAGTTATACTGGATATCTAAGGAAAAGGGAG

AAGTATGGAAACAAAATAAATTTGGGCAAGGAAAGAAAGAGAAAACGCTGGTAGTGAACCCTTGGCTCAC

TCAAGTTCGAATCTTTCATCAACTCAGATACAATAAGTCAGTGCCCAACCTTTGCAAACAGATCTGCAGC

CACCTCTGCCTTCTGAGACCTGGAGGATACAGCTGTGCCTGTCCCCAAGGCTCCAGCTTTATAGAGGGGA

GCACCACTGAGTGTGATGCAGCCATCGAACTGCCTATCAACCTGCCCCCCCCATGCAGGTGCATGCACGG

AGGAAATTGCTATTTTGATGAGACTGACCTCCCCAAATGCAAGTGTCCTAGCGGCTACACCGGAAAATAT

TGTGAAATGGCGTTTTCAAAAGGCATCTCTCCAGGAACAACCGCAGTAGCTGTGCTGTTGACAATCCTCT

TGATCGTCGTAATTGGAGCTCTGGCAATTGCAGGATTCTTCCACTATAGAAGGACCGGCTCCCTTTTGCC

TGCTCTGCCCAAGCTGCCAAGCTTAAGCAGTCTCGTCAAGCCCTCTGAAAATGGGAATGGGGTGACCTTC

AGATCAGGGGCAGATCTTAACATGGATATTGGAGTGTCTGGTTTTGGACCTGAGACTGCTATTGACAGGT

CAATGGCAATGAGTGAAGACTTTGTCATGGAAATGGGGAAGCAGCCCATAATATTTGAAAACCCAATGTA

CTCAGCCAGAGACAGTGCTGTCAAAGTGGTTCAGCCAATCCAGGTGACTGTATCTGAAAATGTGGATAAT

AAGAATTATGGAAGTCCCATAAACCCTTCTGAGATAGTTCCAGAGACAAACCCAACTTCACCAGCTGCTG

ATGGAACTCAGGTGACAAAATGGAATCTCTTCAAACGAAAATCTAAACAAACTACCAACTTTGAAAATCC

AATCTATGCACAGATGGAGAACGAGCAAAAGGAAAGTGTTGCTGCGACACCACCTCCATCACCTTCGCTC

CCTGCTAAGCCTAAGCCTCCTTCGAGAAGAGACCCAACTCCAACCTATTCTGCAACAGAAGACACTTTTA

AAGACACCGCAAATCTTGTTAAAGAAGACTCTGAAGTATAGCTATACCAGCTATTTAGGGAATAATTAGA

AACACACTTTTGCACATATATTTTTTACAAACAGATGAAAAAAGTTAACATTCAGTACTTTATGAAAAAA

ATATATTTTTCCCTGTTTGCCTATAGTTGGAGGTATCCTGTGTGTCTTTTTTTACTTATGCCGTCTCATA

TTTTTACAAATAATTATCACAATGTACTATATGTATATCTTTGCACTGAAGTTGTCTGAAGGTAATACTA

TAAATATATTGTATATTTGTAAATTTTGGAAAGATTATCCTGTTACTGAATTTGCTAATAAAGATGTCTG

CTGATTTGGTTGGTGATCATTATAGTAAATGATCCAACAAGAAAAGGAATTGACTGGGGACCTTTAGCCG

TGTCTAAAGAAGAGGCACCACTCATATTTCCTATAAAATTATCTAGGAAAGGAATCCAGGCCCCGCTCTT

GGGTCCATTTTTACACATTAGCACTTAATTAATGTTCAATATTACATGTCAATTTGATTAATGGCTATGT

TGATAGGGGCCACTATGTGTTGTATAGACATCTGGACTTGACTGTAGACTCCTCAGATAATACAGAAGGT

AGGAAAAGCAATTCAGTTTGGCCCTTCTGTGTGTTGGCATTGTCTAACCAGAACTCTCTGTTTCATGTGT

GTTCTCTCACTAGCTGCCAAGACAACATTTTTATTTGTGATGTCTATGAGGAAATCCCATATCATTAAGT

GCCAGTGTCCTGCATTGAGTTTGTGGTTAATTAAATGAGCTCTTCTGCTGATGGACCCTGGAGCAATTTC

TCCCCTCACCTGACATTCAAGGTGGTCACCTGCCCTAGTAGTTGGAGCTCAGTAGCTGAATTTCTGAAAC

CAAATCTGTGTCTTCATAAAATAAGGTGCAAAAAAAAAAAATACCAGTTAAGTAAAGCCTCAACTGGGTT

TTTGTTTCTATGAAAATATCATTATAATCACTATTTATTTCCTAAGTTGAACCTGAATAGAAAGGGAAAC

CATTCTTATTAAGCTTTTTATTAGGCCCTGTGGCTAAATGTGTACATTTATATTAGAATGTACTGTACAG

TCCAGATCTTTTCTTTAATTCTTATTGGTTTTTTTTTTTTTTTTTTTTTTAGAGATGGAGTCTTGCTATA

TTGCCAAGGCTGATCTTGAAGTCCTGGGCTCAAGTGATCCTCCCACCTCAGCCTCCTGAGTGGTTGGGGT

TACGGGCGTGAGCCACTGTGCCTGGCTTCCAGCTCTCCTCTTAAATAGTGGGTATAGTCTGCACAACAGG

AACCATGGCAGGAATATACACTTTCCCATAGCAAATAGCATACCTGACTCTCTGTGCTAATATTGCACAT

TTGTTAAACAATGAATGAATGGATGGATGGATGGATGGATGAATGAATGAAACATATACTACTGATTATT

TTATTCCAGAGTTCTCAAAATATTTGTTGCTGATATTTTGAGTGCTGACTGTAATTACTTTGATTAGATA

AACAACTGGAAATAATGCTGCTGAAAAAGTTCTAATAAATGTGTATTTTATCAGA(SEQ ID NO.939).

an example of a protein sequence from the above LRP2 mRNA is: (> sp | P98164| LRP2_ human low density lipoprotein receptor-associated protein 2 OS ═ Homo sapiens (Homo sapiens) OX ═ 9606GN ═ LRP2 PE ═ 1 SV ═ 3

MDRGPAAVACTLLLALVACLAPASGQECDSAHFRCGSGHCIPADWRCDGTKDCSDDADEI

GCAVVTCQQGYFKCQSEGQCIPNSWVCDQDQDCDDGSDERQDCSQSTCSSHQITCSNGQC

IPSEYRCDHVRDCPDGADENDCQYPTCEQLTCDNGACYNTSQKCDWKVDCRDSSDEINCT

EICLHNEFSCGNGECIPRAYVCDHDNDCQDGSDEHACNYPTCGGYQFTCPSGRCIYQNWV

CDGEDDCKDNGDEDGCESGPHDVHKCSPREWSCPESGRCISIYKVCDGILDCPGREDENN

TSTGKYCSMTLCSALNCQYQCHETPYGGACFCPPGYIINHNDSRTCVEFDDCQIWGICDQ

KCESRPGRHLCHCEEGYILERGQYCKANDSFGEASIIFSNGRDLLIGDIHGRSFRILVES

QNRGVAVGVAFHYHLQRVFWTDTVQNKVFSVDINGLNIQEVLNVSVETPENLAVDWVNNK

IYLVETKVNRIDMVNLDGSYRVTLITENLGHPRGIAVDPTVGYLFFSDWESLSGEPKLER

AFMDGSNRKDLVKTKLGWPAGVTLDMISKRVYWVDSRFDYIETVTYDGIQRKTVVHGGSL

IPHPFGVSLFEGQVFFTDWTKMAVLKANKFTETNPQVYYQASLRPYGVTVYHSLRQPYAT

NPCKDNNGGCEQVCVLSHRTDNDGLGFRCKCTFGFQLDTDERHCIAVQNFLIFSSQVAIR

GIPFTLSTQEDVMVPVSGNPSFFVGIDFDAQDSTIFFSDMSKHMIFKQKIDGTGREILAA

NRVENVESLAFDWISKNLYWTDSHYKSISVMRLADKTRRTVVQYLNNPRSVVVHPFAGYL

FFTDWFRPAKIMRAWSDGSHLLPVINTTLGWPNGLAIDWAASRLYWVDAYFDKIEHSTFD

GLDRRRLGHIEQMTHPFGLAIFGEHLFFTDWRLGAIIRVRKADGGEMTVIRSGIAYILHL

KSYDVNIQTGSNACNQPTHPNGDCSHFCFPVPNFQRVCGCPYGMRLASNHLTCEGDPTNE

PPTEQCGLFSFPCKNGRCVPNYYLCDGVDDCHDNSDEQLCGTLNNTCSSSAFTCGHGECI

PAHWRCDKRNDCVDGSDEHNCPTHAPASCLDTQYTCDNHQCISKNWVCDTDNDCGDGSDE

KNCNSTETCQPSQFNCPNHRCIDLSFVCDGDKDCVDGSDEVGCVLNCTASQFKCASGDKC

IGVTNRCDGVFDCSDNSDEAGCPTRPPGMCHSDEFQCQEDGICIPNFWECDGHPDCLYGS

DEHNACVPKTCPSSYFHCDNGNCIHRAWLCDRDNDCGDMSDEKDCPTQPFRCPSWQWQCL

GHNICVNLSVVCDGIFDCPNGTDESPLCNGNSCSDFNGGCTHECVQEPFGAKCLCPLGFL

LANDSKTCEDIDECDILGSCSQHCYNMRGSFRCSCDTGYMLESDGRTCKVTASESLLLLV

ASQNKIIADSVTSQVHNIYSLVENGSYIVAVDFDSISGRIFWSDATQGKTWSAFQNGTDR

RVVFDSSIILTETIAIDWVGRNLYWTDYALETIEVSKIDGSHRTVLISKNLTNPRGLALD

PRMNEHLLFWSDWGHHPRIERASMDGSMRTVIVQDKIFWPCGLTIDYPNRLLYFMDSYLD

YMDFCDYNGHHRRQVIASDLIIRHPYALTLFEDSVYWTDRATRRVMRANKWHGGNQSVVM

YNIQWPLGIVAVHPSKQPNSVNPCAFSRCSHLCLLSSQGPHFYSCVCPSGWSLSPDLLNC

LRDDQPFLITVRQHIIFGISLNPEVKSNDAMVPIAGIQNGLDVEFDDAEQYIYWVENPGE

IHRVKTDGTNRTVFASISMVGPSMNLALDWISRNLYSTNPRTQSIEVLTLHGDIRYRKTL

IANDGTALGVGFPIGITVDPARGKLYWSDQGTDSGVPAKIASANMDGTSVKTLFTGNLEH

LECVTLDIEEQKLYWAVTGRGVIERGNVDGTDRMILVHQLSHPWGIAVHDSFLYYTDEQY

EVIERVDKATGANKIVLRDNVPNLRGLQVYHRRNAAESSNGCSNNMNACQQICLPVPGGL

FSCACATGFKLNPDNRSCSPYNSFIVVSMLSAIRGFSLELSDHSETMVPVAGQGRNALHV

DVDVSSGFIYWCDFSSSVASDNAIRRIKPDGSSLMNIVTHGIGENGVRGIAVDWVAGNLY

FTNAFVSETLIEVLRINTTYRRVLLKVTVDMPRHIVVDPKNRYLFWADYGQRPKIERSFL

DCTNRTVLVSEGIVTPRGLAVDRSDGYVYWVDDSLDIIARIRINGENSEVIRYGSRYPTP

YGITVFENSIIWVDRNLKKIFQASKEPENTEPPTVIRDNINWLRDVTIFDKQVQPRSPAE

VNNNPCLENNGGCSHLCFALPGLHTPKCDCAFGTLQSDGKNCAISTENFLIFALSNSLRS

LHLDPENHSPPFQTINVERTVMSLDYDSVSDRIYFTQNLASGVGQISYATLSSGIHTPTV

IASGIGTADGIAFDWITRRIYYSDYLNQMINSMAEDGSNRTVIARVPKPRAIVLDPCQGY

LYWADWDTHAKIERATLGGNFRVPIVNSSLVMPSGLTLDYEEDLLYWVDASLQRIERSTL

TGVDREVIVNAAVHAFGLTLYGQYIYWTDLYTQRIYRANKYDGSGQIAMTTNLLSQPRGI

NTVVKNQKQQCNNPCEQFNGGCSHICAPGPNGAECQCPHEGNWYLANNRKHCIVDNGERC

GASSFTCSNGRCISEEWKCDNDNDCGDGSDEMESVCALHTCSPTAFTCANGRCVQYSYRC

DYYNDCGDGSDEAGCLFRDCNATTEFMCNNRRCIPREFICNGVDNCHDNNTSDEKNCPDR

TCQSGYTKCHNSNICIPRVYLCDGDNDCGDNSDENPTYCTTHTCSSSEFQCASGRCIPQH

WYCDQETDCFDASDEPASCGHSERTCLADEFKCDGGRCIPSEWICDGDNDCGDMSDEDKR

HQCQNQNCSDSEFLCVNDRPPDRRCIPQSWVCDGDVDCTDGYDENQNCTRRTCSENEFTC

GYGLCIPKIFRCDRHNDCGDYSDERGCLYQTCQQNQFTCQNGRCISKTFVCDEDNDCGDG

SDELMHLCHTPEPTCPPHEFKCDNGRCIEMMKLCNHLDDCLDNSDEKGCGINECHDPSIS

GCDHNCTDTLTSFYCSCRPGYKLMSDKRTCVDIDECTEMPFVCSQKCENVIGSYICKCAP

GYLREPDGKTCRQNSNIEPYLIFSNRYYLRNLTIDGYFYSLILEGLDNVVALDFDRVEKR

LYWIDTQRQVIERMFLNKTNKETIINHRLPAAESLAVDWVSRKLYWLDARLDGLFVSDLN

GGHRRMLAQHCVDANNTFCFDNPRGLALHPQYGYLYWADWGHRAYIGRVGMDGTNKSVII

STKLEWPNGITIDYTNDLLYWADAHLGYIEYSDLEGHHRHTVYDGALPHPFAITIFEDTI

YWTDWNTRTVEKGNKYDGSNRQTLVNTTHRPFDIHVYHPYRQPIVSNPCGTNNGGCSHLC

LIKPGGKGFTCECPDDFRTLQLSGSTYCMPMCSSTQFLCANNEKCIPIWWKCDGQKDCSD

GSDELALCPQRFCRLGQFQCSDGNCTSPQTLCNAHQNCPDGSDEDRLLCENHHCDSNEWQ

CANKRCIPESWQCDTFNDCEDNSDEDSSHCASRTCRPGQFRCANGRCIPQAWKCDVDNDC

GDHSDEPIEECMSSAHLCDNFTEFSCKTNYRCIPKWAVCNGVDDCRDNSDEQGCEERTCH

PVGDFRCKNHHCIPLRWQCDGQNDCGDNSDEENCAPRECTESEFRCVNQQCIPSRWICDH

YNDCGDNSDERDCEMRTCHPEYFQCTSGHCVHSELKCDGSADCLDASDEADCPTRFPDGA

YCQATMFECKNHVCIPPYWKCDGDDDCGDGSDEELHLCLDVPCNSPNRFRCDNNRCIYSH

EVCNGVDDCGDGTDETEEHCRKPTPKPCTEYEYKCGNGHCIPHDNVCDDADDCGDWSDEL

GCNKGKERTCAENICEQNCTQLNEGGFICSCTAGFETNVFDRTSCLDINECEQFGTCPQH

CRNTKGSYECVCADGFTSMSDRPGKRCAAEGSSPLLLLPDNVRIRKYNLSSERFSEYLQD

EEYIQAVDYDWDPKDIGLSVVYYTVRGEGSRFGAIKRAYIPNFESGRNNLVQEVDLKLKY

VMQPDGIAVDWVGRHIYWSDVKNKRIEVAKLDGRYRKWLISTDLDQPAAIAVNPKLGLMF

WTDWGKEPKIESAWMNGEDRNILVFEDLGWPTGLSIDYLNNDRIYWSDFKEDVIETIKYD

GTDRRVIAKEAMNPYSLDIFEDQLYWISKEKGEVWKQNKFGQGKKEKTLVVNPWLTQVRI

FHQLRYNKSVPNLCKQICSHLCLLRPGGYSCACPQGSSFIEGSTTECDAAIELPINLPPP

CRCMHGGNCYFDETDLPKCKCPSGYTGKYCEMAFSKGISPGTTAVAVLLTILLIVVIGAL

AIAGFFHYRRTGSLLPALPKLPSLSSLVKPSENGNGVTFRSGADLNMDIGVSGFGPETAI

DRSMAMSEDFVMEMGKQPIIFENPMYSARDSAVKVVQPIQVTVSENVDNKNYGSPINPSE

IVPETNPTSPAADGTQVTKWNLFKRKSKQTTNFENPIYAQMENEQKESVAATPPPSPSLP

AKPKPPSRRDPTPTYSATEDTFKDTANLVKEDSEV(SEQ ID NO.940).

As used herein, "target sequence" refers to a contiguous portion of the nucleotide sequence of an mRNA molecule formed during transcription of a gene of interest, e.g., the CD320 gene or the LRP2 gene, including mRNA that is an RNA processing product that is the major transcription product.

As used herein, the term "sequence-comprising strand" refers to an oligonucleotide comprising a strand of nucleotides described by the sequence referred to using standard nucleotide nomenclature.

"G", "C", "A" and "U" generally represent nucleotides containing guanine, cytosine, adenine and uracil, respectively, as bases. "T" and "dT" are used interchangeably herein and refer to deoxyribonucleotides wherein the nucleobase is a thymine, for example, deoxyribothymine (deoxyribothymidine), 2' -deoxythymidine, or thymidine. However, it will be understood that the terms "ribonucleotide" or "nucleotide" or "deoxyribonucleotide" may also represent a modified nucleotide (as described in further detail below) or an alternative replacement moiety. The skilled artisan will be well aware that guanine, cytosine, adenine and uracil may be replaced by other moieties without substantially altering the base pairing properties of the oligonucleotide, including nucleotides having such replacement moieties. For example, without limitation, a nucleotide comprising inosine as its base may base pair with a nucleotide containing adenine, cytosine, or uracil. Thus, nucleotides containing uracil, guanine, or adenine may be replaced in the nucleotide sequence of the present invention with nucleotides containing, for example, inosine. Sequences containing these replacement parts are embodiments of the present invention.

The term "siRNA" refers to a compound, mixture, composition or agent that contains the RNA of the term as defined herein and mediates targeted cleavage of RNA transcripts by RISC/AGO (RNA-induced silencing complex) complexes, whereby the guide strand of the siRNA hybridizes to its complementary mRNA molecule. The mRNA is degraded by the RISC/AGO complex which has RNase cleavage activity, resulting in mRNA degradation, and the protein encoded by the mRNA is not produced or produced at a reduced level compared to untreated cells. This results in a "knock-down" effect or reduced protein levels of the gene targeted by the siRNA compared to control-treated cells. The siRNA modulates, e.g., inhibits, CD320 in a cell or the expression of LRP2 in a cell, e.g., a cell within a subject, such as a mammalian subject.

In one embodiment, the RNAi agents of the invention comprise single-stranded RNA that interacts with a target RNA sequence, e.g., a CD320 or LRP2 target mRNA sequence, to direct cleavage of the target RNA. Without wishing to be bound by theory, it is believed that long double stranded RNA introduced into cells is broken down into siRNAs by a type III endonuclease known as Dicer (Sharp et al (2001) Genes Dev.15: 485). Dicer (ribonuclease-III-like enzyme) processes dsRNA into 19-23 base pair (bp) short interfering RNA with a characteristic two base 3' overhang (Bernstein, et al, (2001) Nature 409: 363). Initially, siRNA can be composed of two RNA strands, an antisense (or guide) strand and a sense (or passenger) strand, which form a duplex varying in length from 10-80bp with or without a 3' nucleotide overhang. The dsRNA may comprise one or more single-stranded overhangs of one or more nucleotides. In one embodiment, at least one end of the dsRNA has a single-stranded nucleotide overhang of 1 to 4, typically 1 or 2 nucleotides. In another embodiment, the antisense strand of the dsRNA has a 1-10 nucleotide overhang at the 3 'end and 5' end, respectively, on the sense strand. In other embodiments, the sense strand of the dsRNA has a 1-10 nucleotide overhang at the 3 'end and 5' end, respectively, on the antisense strand.

The siRNA is then incorporated into the RNA-induced silencing complex (RISC), where one or more helicases unwind the siRNA duplex, enabling the complementary antisense (guide) strand to guide target recognition (Nykanen, et al, (2001) Cell 107: 309). Once bound to the appropriate target mRNA, one or more endonucleases within the RISC cleave the target to induce silencing (Elbashir, et al, (2001) Genes Dev.15: 188). Thus, in one aspect, the invention relates to single stranded rna (sirna) that is produced within a cell and promotes RISC complex formation to achieve silencing of the target gene, i.e., CD320 or LRP2 gene. Thus, the term "siRNA" is also used herein to refer to RNAi as above.

In another embodiment, the RNAi agent can be a single-stranded siRNA introduced into a cell or organism to inhibit a target mRNA. The single stranded RNAi agent binds to the RISC endonuclease, Argonaute 2, which then cleaves the target mRNA. Single-stranded sirnas are typically 15-80 nucleotides and can be chemically modified to improve metabolic stability and activity; wherein one or more pyrimidine nucleotides may be modified to 2' -deoxy-2 ' -fluoro nucleotides, one or more purine nucleotides may be modified to 2' -deoxy purine nucleotides and further wherein a terminal cap modification may be present at the 3' or 5' end; specifically by the introduction of one or more 2' -deoxythymidine nucleotides or by the introduction of one or more phosphorothioate groups linking any nucleotide in the sequence, but especially any nucleotide at the 3' or 5' end. In addition, a 3' -terminal phosphate or vinylphosphonate group may be introduced. Examples of such modifications would include, but are not limited to, modifications to the ribose moiety of the nucleotide, such as: 2 '-deoxy, 2' -deoxy fluoro, 2 '-methoxy (2' -O-methyl) (Hutvanger et al, (2004) PLOS Biol 2, 0465-. Another modification may be 2' -trifluoromethoxy. Other modifications to the ribose moiety may include bridging modifications whereby the 2 '-carbon of the sugar moiety is covalently linked to the 4' -carbon of the sugar moiety through a methylene or methoxymethylene group to provide bridged nucleotides as LNA and (S) -cET, respectively, in the art (Corey et al, (2018) Nuc Acid Res 46; 1584-. In addition, the sugar moiety may be modified by removing the bond between carbons C2 'and C3' to provide "open" chain nucleotides similar to those in WO 2011/139843 a 2. The ribose moiety of the RNA nucleotide can also be replaced with a morpholino group to provide a PMO nucleotide. Modifications to the phosphodiester portion of a nucleotide are also possible and may include, but are not limited to, the replacement of the phosphodiester group by phosphorothioate and phosphoroamidate (Eckstein et al, (2014) Nuc Acid Therapeutics 24, 374-387). The end of the strand may be modified with 2' -deoxynucleotides, such as dT, and in addition, the dT nucleotide may be modified by a phosphorothioate group instead of the diphosphate. The design and testing of single stranded siRNAs is described in U.S. Pat. No.8,101,348 and Lima et al, (2012) Cell 150: 883-. Any of the antisense nucleotide sequences described herein can be used as described herein or as described by Lima et al, (2012) Cell 150; 883-894.

In another embodiment, "RNAi" for use in the compositions, uses and methods of the invention is double-stranded RNA, and is referred to herein as a "double-stranded RNAi agent," double-stranded RNA (dsRNA) molecule, "" dsRNA agent, "or" dsRNA. The term "dsRNA" refers to a complex of ribonucleic acid molecules having a duplex structure comprising two antiparallel and substantially complementary nucleic acid strands referred to as having "sense" (passenger) and "antisense" (guide) orientations relative to the target RNA, i.e., the CD320 gene or the LRP2 gene. In some embodiments of the invention, double-stranded RNA (dsrna) initiates degradation of a target RNA, e.g., mRNA, by a post-transcriptional gene silencing mechanism referred to herein as RNA interference or RNAi.

Typically, most of the nucleotides of each strand of a dsRNA molecule are ribonucleotides, but as detailed herein, either or both of the two strands may also include one or more non-ribonucleotides, e.g., deoxyribonucleotides and/or modified nucleotides. In addition, as used in the present specification, an "RNAi agent" may include ribonucleotides without chemical modification (Corey et al, (2018) Nuc Acid Res 46; 1584-; RNAi agents can include significant modifications at multiple nucleotides or at a single nucleotide. These modifications may include all types of modifications disclosed herein or known in the art. For the purposes of the present specification and claims, "RNAi agent" encompasses any of these modifications as used in siRNA type molecules. Examples of such modifications would include, but are not limited to, modifications to the ribose moiety of the nucleotide, such as: 2 '-deoxy, 2' -deoxy fluoro, 2 '-methoxy (2' -O-methyl) (Hutvanger et al, (2004) PLOS Biol 2, 0465-. Another modification may be 2' -trifluoromethoxy. Other modifications to the ribose moiety may include bridging modifications whereby the 2 '-carbon of the sugar moiety is covalently linked to the 4' -carbon of the sugar moiety through a methylene or methoxymethylene group to provide bridged nucleotides as LNA and (S) -cET, respectively, in the art (Corey et al, (2018) Nuc Acid Res 46; 1584-. In addition, the sugar moiety may be modified by removing the bond between carbons C2 'and C3' to provide "open" chain nucleotides similar to those in WO 2011/139843 a 2. The ribose moiety of the RNA nucleotide can also be replaced with a morpholino group to provide a PMO nucleotide. Modifications to the phosphodiester portion of a nucleotide are also possible and may include, but are not limited to, the replacement of the phosphodiester group by phosphorothioate and phosphoroamidate (Eckstein et al, (2014) Nuc Acid Therapeutics 24, 374-387). The ends of the sense and antisense strands may be modified with 2' -deoxynucleotides, such as dT, and in addition, dT nucleotides may be modified by phosphorothioate groups instead of diphosphates (fig. 19).

Ribonucleotides can be chemically modified in any single nucleotide or combination of nucleotides in the antisense and sense strands. In some cases, all nucleotides in either the antisense or sense strand or both the antisense and sense strands are chemically modified (Allerson et al, (2005) J Med Chem 48, 901-. In other cases, only some of the nucleotides in either the antisense or sense strand, or in both the antisense and sense strands, are chemically modified (Chiu et al, (2003) RNA 9, 1034-1048). In other cases, the modifications may follow a pattern of alternating 2 '-methoxy and 2' -fluoro modifications to either or both strands of the siRNA and sometimes the complementary nucleotides of the antisense and sense strands may contain non-identical chemical modifications, e.g., where one member of the complementary nucleotide pair has a 2 '-methoxy modification and the other member has a 2' -fluoro modification (Chong et al (2006) Biochem Biophys Res Commun 342, 919-927; Hassler et al, (2018) Nucleic Acid Res 46, 2185-2196).

The two strands forming the duplex structure may be different portions of a larger RNA molecule, or they may be separate RNA molecules. When the two strands are part of a larger molecule, and are thus linked by an uninterrupted nucleotide chain between the 3 '-end of one strand and the 5' -end of the respective other strand forming the double helix structure, the linked RNA strand is referred to as a "hairpin loop". When the two strands are covalently linked by means other than an uninterrupted nucleotide chain between the 3 '-end of one strand and the 5' -end of the respective other strand forming the double helix structure, the linked structure is referred to as a "linker". These RNA strands may have the same or different number of nucleotides. The maximum number of base pairs is the number of nucleotides in the shortest strand of the dsRNA minus any overhang present in the duplex. In addition to the double helix structure, the RNAi agent can comprise one or more nucleotide overhangs.

In one embodiment, the RNAi agents of the invention are 20-30 nucleotide dsrnas that interact with a target RNA sequence, e.g., a CD320 target mRNA sequence or a LRP2 target mRNA sequence, to direct cleavage of the target RNA.

The term "antisense strand" refers to the strand of a double stranded RNAi agent that includes a region substantially complementary to a target sequence (e.g., human CD320 mRNA or LRP2 mRNA). As used herein, the term "region complementary to a portion of an mRNA encoding CD320 or LRP 2" refers to a region on the antisense strand that is substantially complementary to a portion of an mRNA sequence encoding either CD320 or LRP 2. In the case where the regions of complementarity are not fully complementary to the target sequence, mismatches are most tolerated at the terminal regions, and if present they are typically in the terminal regions, e.g., within 6, 5, 4, 3, or 2 nucleotides of the 5 'and/or 3' end. For example, in certain embodiments, substantially complementary can mean that at least 85%, but not all, of the bases in a contiguous sequence of a first polynucleotide in a hybridized pair of nucleobase sequences will hybridize to the same number of bases in a contiguous sequence of a second polynucleotide.

As used herein, the term "sense strand" refers to a dsRNA strand that includes a region that is substantially complementary to a region of the antisense strand.

As used herein, the term "cutting zone" refers to an area located immediately adjacent to the cutting site. The cleavage site is the site on the target where cleavage occurs. In some embodiments, the cleavage region comprises 3 bases on either end of the cleavage site and immediately adjacent thereto. In some embodiments, the cleavage region comprises 2 bases on either end of and immediately adjacent to the cleavage site. In some embodiments, the cleavage site is specifically present at the site bound by nucleotides 10 and 11 of the antisense strand, and the cleavage region comprises nucleotides 11, 12 and 13.

As used herein and unless otherwise indicated, the term "complementary," when used to describe a first nucleotide sequence in relation to a second nucleotide sequence, refers to the ability of an oligonucleotide or polynucleotide comprising the first nucleotide sequence to hybridize and form a duplex structure with an oligonucleotide or polynucleotide comprising the second nucleotide sequence under specific conditions, as will be understood by the skilled artisan. These conditions may, for example, be stringent conditions, wherein stringent conditions may include: 400mM NaCl, 40mM PIPES pH 6.4, 1mM EDTA, 50 ℃ or 70 ℃ for 12-16 hours, and then washed. Other conditions may be applied, such as physiologically relevant conditions that may be encountered inside the organism. For example, the complementary sequence is sufficient to exert the relevant function of the nucleic acid (e.g., RNAi). The skilled person will be able to determine the set of conditions most suitable for testing the complementarity of two sequences, depending on the final application of the hybridized nucleotides.

When a nucleotide of a first nucleotide sequence is base paired with a nucleotide of a second nucleotide sequence over the entire length of the first and second nucleotide sequences, the sequences may be "fully complementary" with respect to each other. However, where a first sequence is referred to herein as "substantially complementary" relative to a second sequence, the two sequences may be perfectly complementary, or they may form one or more, but typically no more than 4, 3 or 2 mismatched base pairs upon hybridization, while retaining the ability to hybridize under conditions most relevant to their end use. However, when two oligonucleotides are designed to form one or more single-stranded overhangs upon hybridization, these overhangs should not be considered mismatches with respect to complementarity determination. For example, for the purposes described herein, such a dsRNA may also be referred to as "fully complementary": the dsRNA comprises one oligonucleotide of 21 nucleotides in length and another oligonucleotide of 23 nucleotides in length, wherein the longer oligonucleotide comprises a sequence of 21 nucleotides that is fully complementary to the shorter oligonucleotide.

As used herein, "complementary" sequences can also include or be formed entirely from non-watson-crick base pairs and/or base pairs formed from non-natural and modified nucleotides, to the extent that the above requirements are met with respect to their hybridization capabilities. Such non-Watson-Crick base pairs include, but are not limited to, G: u wobble base pairing or Hoogstein base pairing.

Herein, the terms "complementary", "fully complementary" and "substantially complementary" may be used with respect to base pairing between the sense strand and the antisense strand of a dsRNA, or between the antisense strand of a dsRNA and a target sequence, as will be understood from the context of its use.

As used herein, a polynucleotide "at least partially substantially complementary" to an mRNA refers to a polynucleotide that is substantially complementary to a contiguous portion (including a 5'UTR, Open Reading Frame (ORF), or 3' UTR) of an mRNA of interest (e.g., an mRNA encoding CD320 or an mRNA encoding LRP 2). For example, a polynucleotide is complementary to at least a portion of a CD320 mRNA or LRP2 mRNA if the sequence is substantially complementary to a non-disrupted portion of the mRNA encoding CD320 or LRP 2.

As used herein, the term "inhibition" is used interchangeably with "reduction", "silencing", "down-regulation", "repression" and other similar terms, and includes any level of inhibition.

As used herein, the phrases "inhibiting expression of CD 320", "inhibiting expression of LRP 2" include inhibiting expression of any CD320 or LRP2 gene (such as a gene identified from, for example, a mouse, rat, monkey, or human) as well as variants (e.g., naturally occurring variants) or mutants of the identified gene. Thus, the CD320 or LRP2 gene may be a wild-type CD320 or LRP2 gene, a mutant CD320 or LRP2 gene, or a transgenic CD320 or LRP2 gene in the context of genetically manipulated cells, cell groups, or organisms.

"inhibiting the expression of the CD320 gene" or "inhibiting the expression of the LRP2 gene" includes any level of inhibition of the CD320 gene or the LRP2 gene, e.g., at least partial inhibition of the expression of the CD320 or LRP2 gene, such as at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% inhibition. In a preferred embodiment, inhibition is assessed by expressing the level of CD320 or LRP2 protein in treated cells as a percentage of the mRNA level in control cells using the following formula:

normalized protein levels of treated cells/normalized protein levels of control cells. Control cells were negative control siRNA. The normalized representation normalizes the protein level to the housekeeping protein level.

Expression of the CD320 or LRP2 genes can be assessed based on the level of any variable associated with CD320 or LRP2 gene expression, e.g., CD320 or LRP2 mRNA levels, CD320 or LRP2 protein levels. Inhibition can be assessed by a decrease in the absolute or relative level of one or more of these variables compared to a control level. The control level can be any type of control level used in the art, e.g., a pre-dose baseline level or a level determined from a similar subject, cell, or sample that is untreated or treated with a control (such as, e.g., a buffer-only control or an inactive agent control).

Contacting a cell with a ds or ss RNAi agent as used herein includes contacting the cell by any possible means, whether in vivo or in vitro. Contacting the cell with the RNAi agent includes contacting the cell with the RNAi agent in vitro or contacting the cell with the RNAi agent in vivo. The contacting may be performed directly or indirectly. Thus, for example, the RNAi agent can be brought into physical contact with the cell by a separate practice, or alternatively, the RNAi agent can be placed in a situation that will allow or allow for subsequent contact with the cell.

As used herein, "patient" or "subject" is intended to include a human or non-human animal, preferably a mammal, e.g., a monkey. Most preferably, the subject or patient is a human.

As used herein, "CD 320-associated diseases" is intended to include any disease associated with interference of the CD320 gene or protein, polymorphisms of the CD320 gene, Single Nucleotide Polymorphisms (SNPs), and epigenetic modifications. Such diseases may be caused, for example, by overproduction of the CD320 protein, by mutation of the CD320 gene, by abnormal cleavage of the CD320 protein, by abnormal folding of the CD320 protein, by abnormal interaction of the CD320 protein with itself or other proteins or other endogenous or exogenous substances. For example, the cancer may be a CD 320-related disease. The degree of inhibition of protein expression can be measured by immunoblotting.

As used herein, "LRP 2-related diseases" is intended to include any disease associated with interference of LRP2 gene, protein, polymorphisms, SNPs and epigenetic modifications of the CD320 gene. Such diseases may be caused, for example, by overproduction of LRP2 protein, by mutation of the LRP2 gene, by abnormal cleavage of the LRP2 protein, by abnormal folding of the LRP2 protein, by abnormal interaction between the LRP2 molecule and other proteins or other endogenous or exogenous substances. For example, the cancer may be an LRP 2-related disease. The degree of inhibition of protein expression can be measured by immunoblotting.

As used herein, "therapeutically effective amount" is intended to include an amount of an RNAi agent sufficient to affect disease treatment (e.g., by reducing, ameliorating, or maintaining one or more symptoms of an existing disease or disease, or by preferentially causing death of disease cells as compared to non-disease cells) when administered to a cell or patient for treatment of a CD 320-associated disease or LRP 2-associated disease. The "therapeutically effective amount" may be different based on the RNAi agent, how the agent is administered, the disease and its severity and history, age, body weight, family history, genetic makeup, stage of the pathological process mediated by CD320 or LRP2 expression, type of prior or concomitant therapy (if any), and other individual characteristics of the patient to be treated.

As used herein, a "prophylactically effective amount" is intended to include an amount of an RNAi agent that is sufficient to prevent or ameliorate one or more symptoms of a disease or pathogen when administered to a subject who has not experienced or exhibited symptoms of a CD 320-associated disease or LRP 2-associated disease, but who is susceptible to disease. Ameliorating a disease includes slowing the course of the disease or reducing the severity of the disease that occurs later. The "prophylactically effective amount" may be different based on the RNAi agent, how the agent is administered, the degree and history of risk of the disease, age, weight, family history, genetic makeup, type of prior or concomitant therapy (if any), and other individual characteristics of the patient to be treated.

"therapeutically-effective amount" or "prophylactically-effective amount" also includes the amount of RNAi agent that produces some desired local or systemic effect at a reasonable benefit/risk ratio applicable to any treatment. The RNAi agents used in the methods of the invention can be administered in amounts sufficient to produce a reasonable benefit/risk ratio applicable to such treatment.

Pharmaceutical composition

The methods described herein include administration of an LRP2 inhibitory composition and/or a CD320 inhibitory composition, e.g., a first siRNA targeting the CD320 gene and/or a second siRNA targeting the LRP2 gene. In some embodiments, the LRP2 inhibiting composition and/or the CD320 inhibiting composition is a pharmaceutical composition.

The methods described herein also include administration of one or more LRP2 inhibitory compositions and/or one or more CD320 inhibitory compositions, e.g., one or more sirnas targeting the CD320 gene and/or one or more sirnas targeting the LRP2 gene. It is understood that these compositions can be chemically modified in a variety of ways and that these modifications need not be the same in the compositional mixture. In some embodiments, the LRP2 inhibiting composition and/or the CD320 inhibiting composition is a pharmaceutical composition.

The pharmaceutical compositions of the present invention may be administered in a variety of ways depending on whether local or systemic treatment is desired and depending on the area to be treated. Administration can be topical, pulmonary, e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal, intranasal, epidermal and transdermal, oral or parenteral administration. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranial, e.g., intraparenchymal, intrathecal, or intraventricular administration.

The composition can be delivered in a manner that targets a particular tissue, such as a lung cell, or a breast cell, or a brain cell, or a bladder cell, or a uterine cell, or a cervical cell, or a prostate cell. The pharmaceutical composition may be delivered by direct injection into the brain. The injection can be by stereotactic injection to a specific region of the brain (e.g., substantia nigra, cortex, hippocampus, striatum, or globus pallidus), or the dsRNA can be delivered to multiple regions of the central nervous system (e.g., multiple regions of the brain, and/or spinal cord). dsRNA can also be delivered to discrete regions of the brain (e.g., discrete delivery to the cortex of the brain). Typically, the siRNA is administered 1) by intratumoral injection, 2) by systemic injection, 3) by sustained release from the implanted polymer. Other tissue specificities can be achieved by antibody or small molecule conjugation or by tissue-specific delivery devices (e.g., a catheter can be used for delivery to the bladder).

In one embodiment, RNAi targeting LRP2 or CD320 can be delivered through a cannula or other delivery device implanted into tissue at one end. The cannula may be connected to a reservoir of RNAi composition. Flow or delivery may be regulated by a pump, for example, an osmotic pump or a micropump. In one embodiment, the pump and reservoir are implanted in a region remote from the tissue, e.g., the abdomen, and delivery is effected by a conduit leading from the pump or reservoir to the release site.

Thus, in some embodiments, a pharmaceutical composition described herein includes one or more pharmaceutically acceptable excipients. The pharmaceutical compositions described herein are formulated for administration to a subject.

As used herein, a pharmaceutical composition or medicament includes a pharmacologically effective amount of at least one of the RNAi agents described and one or more pharmaceutically acceptable excipients. Pharmaceutically usable excipients (excipients) are substances other than the active pharmaceutical ingredient (API, therapeutic product, e.g. CD320 RNAi agent or LRP2 RNAi agent) which are intended to be comprised in a drug delivery system. The excipients are not present in the desired dosage or are not intended to exert a therapeutic effect. The excipients may function to a) aid in the processing of the drug delivery system during manufacture, b) protect, support or improve the stability, bioavailability or patient acceptance of the API, c) aid in product identification, and/or d) improve any other attribute of the overall safety, effectiveness of delivery of the API during storage or use. Pharmaceutically acceptable excipients may or may not be inert substances.

Excipients include (but are not limited to): absorption enhancers, anti-adherents, anti-foaming agents, anti-oxidants, binders, buffers, carriers, coatings, pigments, delivery enhancers, delivery polymers, dextrans, dextrose, diluents, disintegrants, emulsifiers, bulking agents, fillers, flavors, glidants, diluents, lubricants, oils, polymers, preservatives, saline, salts, solvents, sugars, suspending agents, sustained release matrices, sweeteners, thickeners, tonicity agents, vehicles, water repellents, and wetting agents.

Pharmaceutical compositions suitable for injectable use may include sterile aqueous solutions (when water-soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, cremophor.rtm.eltm (BASF, Parsippany, n.j.) or Phosphate Buffered Saline (PBS). The compositions, including formulations and drug delivery systems, are believed to be stable under manufacturing and storage conditions and should be protected from contaminating action against microorganisms, such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol), and suitable mixtures thereof. Proper fluidity can be maintained, for example, by the use of a coating, such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. In most cases, it will be preferred to include isotonic agents, for example, sugars, polyols such as mannitol, sorbitol, and sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

Sterile injectable solutions can be prepared by incorporating the active compound in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, following filtered sterilization. Generally, dispersions are prepared by incorporating the active compound in a sterile vehicle which contains the basic dispersion vehicle and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods of preparation include vacuum drying and freeze-drying which yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

Formulations suitable for intra-articular administration may be in the form of a sterile aqueous formulation of the drug, which may be in microcrystalline form, e.g., in the form of a microcrystalline aqueous suspension. Liposomal formulations or biodegradable polymer systems may also be used to provide drugs for intra-articular and ophthalmic administration.

The active compound can be prepared with carriers that will protect the compound from rapid elimination from the body, such as controlled release formulations, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid may be used. Methods of preparing these formulations will be apparent to those skilled in the art. Liposomal suspensions may also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No.4,522,811.

Dosage and timing

The skilled artisan will appreciate that certain factors may influence the dosage and timing required to effectively treat a subject, including, but not limited to, the severity of the disease or disorder, previous treatments, the general health and/or age of the subject, and other diseases present. In addition, treatment of a subject with a therapeutically effective amount of the composition may comprise a single treatment or a series of treatments. Effective dosages and in vivo half-lives of LRP2 inhibitory compositions and/or CD320 inhibitory compositions encompassed by the invention can be estimated using conventional methods or based on in vivo testing using appropriate animal models, as described elsewhere herein.

Generally, suitable dosages of pharmaceutical compositions of the LRP2 inhibitory composition and/or the CD320 inhibitory composition will be in the range of 0.01 to 300.0 mg per kg body weight of the receptor per day, typically in the range of 1 to 50mg per kg body weight per day.

For example, the LRP2 inhibiting composition and/or the CD320 inhibiting composition can be an siRNA composition of one or more siRNAs, and can be administered at 0.01mg/kg, 0.05mg/kg, 0.2mg/kg, 0.3mg/kg, 0.4mg/kg, 0.5mg/kg, 0.6mg/kg, 0.7mg/kg, 0.8mg/kg, 0.9mg/kg, 1mg/kg, 1.1mg/kg, 1.2mg/kg, 1.3mg/kg, 1.4mg/kg, 1.5mg/kg, 1.628mg/kg, 2mg/kg, 3mg/kg, 5.0mg/kg, 10mg/kg, 20mg/kg, 30mg/kg, 40mg/kg, 50mg/kg, 100mg/kg, 200mg/kg, 400mg/kg per single dose. In another embodiment, the dose is between 0.15mg/kg and 0.3 mg/kg. For example, LRP2 and/or CD320 inhibitory compositions may be administered at a dose of 0.15mg/kg, 0.2mg/kg, 0.25mg/kg, or 0.3 mg/kg. In one embodiment, the LRP2 and/or CD320 inhibitory composition is administered at a dose of 0.3 mg/kg.

The pharmaceutical composition may be administered once daily, or once or twice every 5, 10, 15, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days. The dosage units may be mixed for delivery over several days, e.g., using conventional sustained release formulations that provide sustained release of the LRP2 inhibitory composition and/or the CD320 inhibitory composition over a period of several days. Sustained release formulations are well known in the art and are particularly useful for the delivery of agents at specific sites, as may be used with the agents of the present invention.

In one embodiment, the LRP 2-inhibiting composition and/or the CD 320-inhibiting composition is tumor cell line dependent and is at a dose of 0.3mg/kg, and wherein the dose is administered once every 21 days. In another embodiment, the effective amount is 0.3mg/kg and is administered every 21 days by a 70 minute infusion of 1mL/min, 15 minutes, then 3mL/min, 55 minutes. In another embodiment, the effective amount is 0.3mg/kg and is administered by a 60 minute infusion of 3.3mL/min, or by a 70 minute infusion of 1.1mL/min, 15 minutes, then 3.3mL/min, 55 minutes, at two doses every 21-28 days.

For treatment, the dosage of the LRP2 inhibiting composition and/or the CD320 inhibiting composition may be adjusted.

The LRP2 inhibitory composition and/or the CD320 inhibitory composition may be administered in combination with other known agents effective in the treatment of pathological processes mediated by target gene expression.

In another embodiment, the pharmaceutical composition is formulated for administration according to a dosage regimen described herein, e.g., no more than once every 4 weeks, no more than once every 3 weeks, no more than once every two weeks, or no more than once every week. In another embodiment, administration of the pharmaceutical composition may be maintained for one month or more, e.g., 1, 2, 3, or 6 months or one year or more.

In embodiments of the pharmaceutical compositions described herein, the RNAi (e.g., dsRNA) is administered with a buffered solution. In embodiments, the buffer solution comprises acetate, citrate, prolamine, carbonate, or phosphate, or any combination thereof. In embodiments, the buffer solution is Phosphate Buffered Saline (PBS).

In embodiments of the pharmaceutical compositions described herein, the composition is administered intravenously.

In embodiments of the pharmaceutical compositions described herein, the composition is administered subcutaneously.

In certain embodiments, a pharmaceutical composition, e.g., a composition described herein, comprises a lipid formulation. In an embodiment, the composition is administered intravenously.

In some embodiments, a pharmaceutical composition, e.g., a composition described herein, comprises a cationic polyamine formulation or nanoparticle (e.g., JetPEI). In some embodiments, the composition is administered intravenously.

In another embodiment, the pharmaceutical composition is formulated for administration according to a dosage regimen described herein, e.g., no more than once every 4 weeks, no more than once every 3 weeks, no more than once every two weeks, or no more than once every week. In another embodiment, administration of the pharmaceutical composition may be maintained for one month or more, e.g., 1, 2, 3, or 6 months or one year or more.

In another embodiment, a composition comprising an RNAi agent, e.g., dsRNA targeting LRP2 or CD320, featured in the invention is administered with a non-RNAi therapeutic agent, such as an agent known to treat cancer, e.g., lung cancer. In another embodiment, a composition comprising an RNAi agent featured in the invention, e.g., a dsRNA targeting LRP2 and/or CD320, is administered with a non-RNAi treatment regimen, such as radiation therapy, chemotherapy, immunotherapy, photodynamic therapy, or a combination thereof.

In one aspect, provided herein is a method of inhibiting expression of LRP2 and/or CD320 in a cell, the method comprising: (a) introducing an RNAi agent (e.g., dsRNA) described herein into the cell and (b) maintaining the cell of step (a) for a time sufficient to obtain degradation of mRNA transcripts of the LRP2 gene and/or the CD320 gene, thereby inhibiting expression of the LRP2 gene and/or the CD320 gene in the cell.

In one aspect, provided herein are methods for reducing or inhibiting expression of the LRP2 gene and/or the CD320 gene in a cell. The method comprises the following steps: (a) introducing into a cell one or more complementary double-stranded ribonucleic acid (dsRNA) molecules, wherein one sequence is represented as a sense strand and the other sequence is represented as an antisense strand, and wherein the antisense strand has substantial complementarity to a portion of an mRNA encoding LRP2 or CD 320. The region of complementarity is 15-30 nucleotides in length, and typically 19-24 nucleotides in length, and once in a cell expressing LRP2 and/or CD320, the dsRNA inhibits expression of LRP2 protein and/or CD320 protein by at least 10%, e.g., at least 20%, at least 30%, at least 40% or more; (b) single or repeated treatment of cells with dsRNA as described in part (a) to maintain at least 10%, e.g., at least 20%, at least 30%, at least 40% or more inhibition of LRP2 and/or CD320 protein expression over a desired period of time.

In embodiments of the above methods of inhibiting the expression of LRP2 and/or CD320 in a cell, the cell is treated ex vivo, in vitro, or in vivo. In embodiments, the cell is melanoma, glioblastoma, lung, triple negative breast, kidney, pancreas, hepatocellular, ovary, and prostate.

In some embodiments, the cell is present in a subject in need of treatment, prevention, and/or management of a CD 320-related disease or an LRP 2-related disease.

In an embodiment, expression of LRP2 and/or CD320 is inhibited by at least 30%.

In embodiments, IC of RNAi (e.g., dsRNA)₅₀In the range of 0.01-50 nM.

In embodiments, IC of RNAi (e.g., dsRNA)₅₀In the range of 0.01-1 nM.

In certain embodiments, the cell is a mammalian cell (e.g., a human, non-human primate, or rodent cell).

In one embodiment, the cells are treated ex vivo, in vitro, or in vivo (e.g., the cells are present in a subject (a patient in need of treatment, prevention, and/or control of a disorder associated with LRP2 and/or CD320 expression)).

In one embodiment, the subject is a mammal (e.g., a human) at risk for or diagnosed with a proliferative disorder.

In embodiments, the RNAi (e.g., dsRNA) is formulated as a Lipid Nanoparticle (LNP) polyplex (polyamine) formulation.

In embodiments, the RNAi (e.g., dsRNA) is administered at a dose of 0.05001-500.01 mg/kg.

In embodiments, the RNAi (e.g., dsRNA) is administered at a concentration of 0.01mg/kg to 50.1mg/kg of subject body weight.

In embodiments, the RNAi (e.g., dsRNA) is formulated as an LNP formulation and administered at a dose of 0.050.1-50.5 mg/kg.

In embodiments, IC of RNAi (e.g., dsRNA)₅₀At 0.0In the range of 1-10 nM.

In embodiments, RNAi (e.g., dsRNA) or a composition comprising RNAi is administered according to a dosage administration regimen. In embodiments, the RNAi (e.g., dsRNA) or composition comprising RNAi is administered as a single dose or in multiple doses, e.g., according to a dosage administration regimen.

As used herein, the term "sample" includes a collection of fluids, cells, or tissues isolated from a subject as well as fluids, cells, or tissues present within a subject. Examples of biological fluids include blood, serum and serosal fluids, plasma, cerebrospinal fluid, ocular fluids, lymph, urine, saliva, and the like. The tissue sample may comprise a sample from a tissue, organ or localized region. For example, the sample may be derived from a particular organ, organ portion, or fluid or cells within those organs. In certain embodiments, the sample may be derived from a tumor. In a preferred embodiment, a "subject-derived sample" refers to blood or plasma drawn from a subject. In other embodiments, a "sample derived from a subject" refers to a tissue biopsy derived from the subject.

In one embodiment, a characteristic RNAi (e.g., dsRNA) herein comprises a first sequence of a dsRNA selected from the sense sequences of table 1 and a second sequence selected from the corresponding antisense sequences of table 1. It is understood that the suffix a (e.g., OSC17A) represents the antisense strand, whereas the suffix S (e.g., OSC17S) represents the sense strand. In those cases when we refer to siRNA without a suffix (e.g., OSC17), we mean referring to dsRNA including the antisense and sense strands corresponding to that number (e.g., OSC17A paired with OSC 17S).

In some embodiments, the RNAi is about 15 to about 25 nucleotides in length, and in other embodiments, the RNAi is about 25 to about 30 nucleotides in length. Once contacted with a cell expressing CD320, RNAi targeting CD320 inhibits expression of the CD320 gene by at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% or more, as determined by the methods as described herein. In one embodiment, the RNAi targeting CD320 is formulated in a Stable Nucleic Acid Lipid Particle (SNALP).

In some embodiments, the RNAi is about 15 to about 25 nucleotides in length, and in other embodiments, the RNAi is about 25 to about 30 nucleotides in length. Once contacted with cells expressing LRP2, RNAi targeting LRP2 inhibited the expression of LRP2 gene by at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% or more, as determined by the methods as described herein. In one embodiment, RNAi targeting LRP2 is formulated in a Stable Nucleic Acid Lipid Particle (SNALP).

In some embodiments, the RNAi is about 15 to about 25 nucleotides in length, and in other embodiments, the RNAi is about 25 to about 30 nucleotides in length. Once contacted with a cell expressing CD320, RNAi targeting CD320 inhibits expression of the CD320 gene by at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% or more, as determined by the methods as described herein. In one embodiment, the CD 320-targeted RNAi is formulated as a complex, which may be present as nanoparticles with cationic polyamines.

In some embodiments, the RNAi is about 15 to about 25 nucleotides in length, and in other embodiments, the RNAi is about 25 to about 30 nucleotides in length. Once contacted with cells expressing LRP2, RNAi targeting LRP2 inhibited the expression of LRP2 gene by at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% or more, as determined by the methods as described herein. In one embodiment, RNAi targeting LRP2 is formulated as a complex, which may be present as a nanoparticle with a cationic polyamine.

Referring now to table 1-shRNA sequences used in lentiviral vectors, sequences for targeting CD320 sequences encoding CD320 protein and LRP2 sequences encoding LRP2 protein are shown. The sequences in table 2 show DNA that is subsequently transcribed into shRNA, which thus targets the CD320 or LRP2 mRNA for destruction in cells. Each vector carrying the shRNA coding sequence also contains a unique resistance gene that will enable selection of those cells that take up the shRNA, since those cells that do not take up the shRNA with the unique resistance gene will not survive. On day 2, drug selection was started. On day 3, cells were harvested and plated in new dishes. Only cells with the drug resistance gene, i.e. cells that have taken up shRNA virions, will survive this replating procedure. From day 4 onwards, the growth of each cultured cell was closely observed. As expected, cells infected with an irrelevant control shRNA will continue to grow (because shRNA is essentially a non-functional shRNA) -data not shown. The results for cell lines that absorbed CD320+ LRP2 shRNA are shown in table 1.

TABLE 1

Preliminary studies showed that cancer cells were selectively killed by CD320 and LRP2 knockdown, while normal cells were unaffected (table 2).

Table 2 shows the effect of simultaneous knockdown of CD320 and LRP2 on cell viability.

TABLE 2

Other cancer cell lines were also treated with the compounds described herein to determine whether the cancer cell lines were more sensitive to growth inhibition and toxicity than non-cancer cells of the same origin. Cell lines from skin, prostate and brain cancers were screened similarly to the experimental summary in figure 1. Table 3 summarizes the effect of simultaneous knockdown of CD320 and LRP2 in cancer and normal cells.

TABLE 3

Cells were unaffected compared to shSCR (control)

Cells were moderately affected compared to shSCR (control)

+ cells were significantly affected compared to shSCR (control)

0 most cells were killed compared to shSCR (control)

The screening results showed that by simultaneous knockdown of CD320 and LRP2 ("double knockdown"), lung, prostate, skin and brain cancer cell lines were growth-inhibited or killed, while non-cancer cells were unaffected.

Referring now to fig. 2, representative photographs of cells were taken to record their phenotypes after double knockdown of CD320 and LRP2 and to show the sensitivity of cancer cell lines to knockdown of CD320 and LRP2 protein expression.

Normal cells (GM05659 fibroblasts) or cancer cells were infected with lentiviruses expressing either the control sequence or shRNA of shCD320 and shLRP2, as shown in fig. 1. Cells were grown as depicted in FIG. 1. At day 9 post-lentivirus transfection, photographs of the cells were taken. The solid oval represents healthy growth of normal fibroblasts infected with shRNA against CD320 and LRP 2. The dashed ovals represent unhealthy dying cells of cancer cell lines infected with shRNA against CD320 and LRP 2.

These results support the use of the compounds as therapeutic agents, based on the fact that decreased expression of CD320 and LRP2 proteins preferentially leads to adverse effects in cancer cells compared to non-cancer cells. The original experiment was performed using shRNA delivered by lentiviral vectors. Short inhibitory rnas (sirnas) having sequences partially complementary to CD320 protein and/or LRP2 protein were designed. Sirnas can be chemically modified to increase their stability and potency and reduce their immunogenicity, and there are a number of platforms for their delivery in clinical applications.

siRNA sequences that effectively knock down the protein levels of LRP2 and/or CD320 were designed and identified. Table 4 is a list of siRNA sequences complementary to mRNA of CD320 or LRP2, which were tested for their ability to knock down CD320 or LRP2 protein, respectively (see figure 3, figure 4, figure 5, figure 12 and figure 15).

TABLE 4

The list of all possible siRNA sequences is quite large. We have identified 340 possible siRNA sequences against LRP2 and 59 possible siRNA sequences against CD320 (for a complete list, see tables 5 and 6, and tables 5A and 6A identify the target location and the sequence complementary to each identified antisense sequence). In addition, these siRNA sequences can be chemically modified to improve their stability and reduce their off-target effects. siRNA molecules are vulnerable to metabolic degradation, for example, by rnases or dnases. Chemical modification of siRNA molecules by incorporating one or more non-natural (i.e., artificial) nucleotides within the sequence can confer tolerance to such metabolic degradation to the siRNA and increase their biological half-life in cells or in plasma. In addition, inclusion of artificial nucleotides at strategic positions within the siRNA sequence can reduce the immunogenicity of the siRNA and improve selectivity for the guide strand relative to the passenger strand. The modified siRNA molecule may incorporate a single type of artificial nucleotide or may comprise a plurality of different types of artificial nucleotides. Artificial nucleotides can include, but are not limited to, those containing chemical modifications to the ribose moiety or to the phosphate moiety (fig. 19 and table 7). Examples of artificial nucleotides include, but are not limited to, the structures shown in table 7. In addition, modifications of multiple structural elements may be combined. In addition, nucleobase B can be modified, in addition to the natural RNA nucleobase (G, C, A, U), the modification can include non-natural bases, such as those containing sulfur atoms (e.g., thiouracil).

TABLE 7 nucleotide modifications corresponding to FIG. 19A

Name (R)a

Y

X

Z

R

R’

B (nucleobases)

[2fN]

O

O

O

F

H

G. C, A, U, others

2’-FANA

O

O

O

H

F

G. C, A, U, others

[mN]

O

O

O

OMe

H

G. C, A, U, others

2’-MOE

O

O

O

CH2CH2OMe

H

G. C, A, U, others

2’-EA

O

O

O

CH2CH2NH2

H

G. C, A, U, others

2’-DMEA

O

O

O

CH2CH2NMe2

H

G. C, A, U, others

2’-DMAP

O

O

O

CH2CH2CH2NMe2

H

G. C, A, U, others

E.g. N1N 2

O

S

O

OH

H

G. C, A, U, others

As in N1N 2

S

S

O

OH

H

G. C, A, U, others

2' -deoxy

O

O

O

H

H

G. C, A, U, others

4’-S

O

O

S

H

H

G. C, A, U, itIt is composed of a base, a cover and a cover

F-SRNA

O

O

S

F

H

G. C, A, U, others

Me-SRNA

O

O

S

OMe

H

G. C, A, U, others

4’-S-FANA

O

O

S

H

F

G. C, A, U, others

^aN represents any ribonucleotide or deoxyribonucleotide or an analogue thereof.

In some embodiments, a phosphodiester group covalently linking two nucleotides is chemically modified such that, for example, one or both oxygen atoms in the group are replaced with a sulfur atom, as indicated by a single or double asterisk between the two nucleotides to indicate that one or both oxygen atoms in the phosphodiester are replaced with sulfur (table 7 and fig. 19A). In some embodiments, the siRNA sequence may include other artificial nucleotides in which the ribose moiety has been further structurally modified, such as the addition of a bridging atom covalently linking carbons 2 'and 5' of the ribose moiety (fig. 19B-C) or positions 1 'and 2' of the ribose moiety (fig. 19D), or alternatively, a change in the size of the sugar ring in a given nucleotide, e.g., a deletion of the bond between carbons 2 'and 3' of the ribose moiety (fig. 19E) or an increase in the size of the sugar ring from 5 to 6 atoms (fig. 19F-G).

TABLE 5 CD320

TABLE 6 LRP2

TABLE 5A CD320 antisense target

TABLE 6A LRP2 antisense targets

In some embodiments, the antisense strand (denoted by "a" in the OS ID name) and/or the sense strand (denoted by "S" in the OS ID name) of the RNAi agent comprises or consists of a nucleobase sequence, e.g., "OSC 17A-1" CAGUUGCGCAGUUUCUUGUCAGUUC [ dT ] (SEQ ID NO: 17), and the nucleobase sequence may comprise at least one or more nucleotides as modified nucleotides, and wherein the nucleobase sequence of SEQ ID NO: 17 are located at positions 1 to 25(5'→ 3') of the antisense strand and form a double helix with the corresponding sense strand (denoted OSC 17S-1). In some embodiments, the antisense strand of the RNAi agent comprises or consists of a nucleobase sequence (e.g., CAGUUGCGCAGUUUCUUGUCAGUUC [ dT ] (SEQ ID NO: 17)), wherein all or substantially all or 1, 2, 3, 4, or 5 nucleotides are modified nucleotides (see, e.g., SEQ ID No.24), and wherein the nucleobase sequence of SEQ ID NO: 24 are located at positions 1 to 27(5'→ 3') of the antisense strand. For any of the antisense or sense strands disclosed herein, in some embodiments, the antisense strand of the RNAi agent comprises or consists of the sequence (5'→ 3') wherein: (t) is a phosphorothioate linkage between deoxythymines [ dT ]; and/or wherein mC, mA, mG and mU are respectively 2 '-O-methylcytidine, 2' -O-methyladenine, 2 '-O-methylguanosine and 2' -O-methyluridine; and/or wherein 2fA, 2fU, 2fG, 2fC are 2 '-fluoroadenine, 2' -fluorouracil, 2 '-fluoroguanosine, and 2' -fluorocytosine, respectively. Antisense targets on mRNA are denoted by the same name, but do not denote "a" or "S" after the name. Antisense sequences having the same name, for example, OSC17A-1 through OSC17A-18 bind to the same nucleotide target sequence.

The sequences shown in table 4 were transfected into HEK293 (human embryonic kidney) and MDA-MB-435S (human melanoma) cell lines to determine their ability to reduce protein expression of LRP2 and CD320 genes/proteins. Due to their relatively high expression levels of LRP2, both cell lines were selected, as mentioned in the Human Protein map (Human Protein Atlas) on world wide web Protein Atlas. org and in the NCI-60 gene expression profile on disc. nc. nih. gov/cell mininer/, to easily detect changes in Protein expression of LRP 2.

Referring now to FIGS. 3A-B and 3D-E, HEK293 and MDA-MB-231 cells were transfected with siRNA as indicated at 20nM and incubated for 48 hours. Whole cell lysates were prepared and immunoblotted for CD320 and LRP2 protein levels. Protein levels were normalized to housekeeping control genes that were not affected by siRNA transfection. The figure shows the fold change in protein levels compared to a missense siRNA control (OSS 1). (mean-/+ SEM, n ═ 3 is shown).

CD320 and LRP2 protein levels were determined by immunoblotting and quantified by Image Studio Software (LiCor Company) relative to control proteins not affected by CD320 or LRP2 knockdown. To determine the knockdown efficiency, the protein levels of CD320 (fig. 3A-B) and LRP2 (fig. 3D-E) on samples exposed to siRNA sequences of the mRNA of either gene were compared to the levels in untreated and missense controls (black and gray bars, respectively, in all of the figures of fig. 3). We found that both siRNA sequences (OSC17 and OSC47) directed against CD320 almost completely terminated the expression of CD320 (circles in fig. 3A-B). The siLRP2 sequence resulted in a different reduction in the efficiency of the LRP2 protein. In both cell lines, both sequences (OSL231 and OSL245) consistently reduced LRP2 levels by 75% or more (fig. 3B, circle of E).

Referring now to fig. 6, lysates were prepared from transformed (HEK293) and representative cancer cell lines and immunoblots were performed to determine LRP2 protein levels. The cancer cells screened had low LRP2 expression levels. Results represent the mean + SEM of 3 independent lysates. The data indicate that the cancer cells screened have very low expression levels of LRP 2.

We transfected a panel of LRP2 and CD320 sirnas into cancer cell lines derived from various tissues and analyzed the levels of LRP2 protein and CD320 protein in the cell lines. Representative cell lines from prostate, breast and glioblastoma, as well as normal fibroblasts, were exposed to siRNA against CD320 and LRP2 in an experimental design similar to that described for HEK293 and MDA-MB-435S cells. The results are shown in fig. 3C, F and 4.

Reference is now made to fig. 3C, F; and figure 4, MDA-MB-231LnCAP, MCF-7, and U251 cells were exposed to siRNA sequences to knock down CD320 (figure 3C and figures 4A-C) and LRP2 (figures 3F and 4D-F) in a similar manner as described for the data shown in figures 3A, B, D, and E. CD320 protein was knocked down by more than 90% for all cell lines tested, compared to untreated or missense controls, fig. 3C and fig. 4A-C. LRP2 knockdown was also accomplished in all cell lines. However, the knockdown level in LnCAP cells was lower compared to another cell line, and the effective sequences could also be different (fig. 3F and fig. 4D-F).

Referring now to fig. 5, an experimental design similar to that described in fig. 3 was used. Other prostate and brain cancer cell lines as well as normal fibroblasts were exposed to siRNA against CD 320. CD320 levels in DU-145 (prostate) cells were nearly terminated, while knockdown levels in a172 brain cells and normal fibroblasts were 21% -33% and 25% -28%, respectively (fig. 5A-C).

From these studies we can conclude that two sirnas against CD320 (OSC17 and OSC47) were very effective at knocking down CD320 protein levels (80% or more) in almost every cell line tested. Although LRP2 is theoretically more difficult to knock down due to its size, we have identified two sirnas, OSL231 and OSL245, which consistently knock down LRP2 in most cell lines where we can detect LRP 2.

In addition, LRP2 protein was expressed at high levels in HEK293 cells and was readily detectable by immunoblotting. Cancer cell lines had much lower LRP2 expression compared to HEK293 cells (fig. 6), as measured by immunoblotting, and some cell lines could contain LRP2 at levels that were reliably detectable below.

Referring now to fig. 7, the effect of doxorubicin treatment on cell viability as measured by the CTG assay is shown. A172 and HCC15 cells were plated at 1200 cells/well in 96-well plates. The following day, cells were treated with doxorubicin at the indicated concentrations. The viability of the cells was determined using the CTG assay 4 days after the onset of doxorubicin exposure. Line representation computing IC ₅₀Non-linear fit of the data of values. Instead of visual assessment of the effect of knockdown of CD320/LRP2 gene expression on cell proliferation (as shown in figure 2 for shRNA-mediated knockdown of CD320/LRP 2), a functional assay for quantifying the effect of simultaneous knockdown of LRP2 and CD320 by siRNA was developed. A widely used assay for Cell viability measurement is Promega Cell-titerPlatform (CTG) which quantifies ATP levels in cells (ATP produced by live cells, not dead cells). After incubation of the cells with CTG reagents, ATP levels can be measured indirectly using a TECAN luminescence microplate reader as light production. As a first step, the toxicity of the known chemotherapeutic drug doxorubicin was determined for the cell line of interest. In our assay, doxorubicin was used as a positive control for cytotoxicity. Figure 7 shows representative data from a172 brain cancer cells (figure 7A) and HCC15 lung cancer cells (figure 7B) exposed to doxorubicin. From this data, the IC of doxorubicin treatment on these cell lines was determined₅₀: a172 cells were 132nm and HCC15 cells were 167 nm. Based on these findings, a larger screen was initiated to determine the IC of doxorubicin in several cancer and non-cancer cell lines ₅₀To determine when the cell line was used in a simultaneous knockdown viability assay testing CD320 and LRP2,dosage of doxorubicin. IC at Table 8 doxorubicin₅₀The results of the cell lines tested are summarized in the determination.

To quantify the effect of knockdown of CD320 and LRP2 on cell proliferation, cells were plated in 24-well plates. The next day, cells were transfected with sirnas against CD320 and/or LRP 2. For effective toxicity, cell lines may require repeated transfections and/or times (cell line dependent). In this experimental design, there is room for re-infection and some cell lines are required for effective toxicity. At the end of the study, cell growth of the cell lines was analyzed by CTG assay. A schematic of this experimental design is shown in figure 8.

TABLE 8

Cell lines were plated at 1,000 to 4,000 cells/well in 96-well plates and treated with doxorubicin the following days. CTG activity was measured 4 days after treatment. IC calculation by GraphPad Prism software₅₀The value is obtained. The results are summarized in table 8.

These data show that doxorubicin works effectively on this CTG platform (i.e., doxorubicin kills cancer cells) and therefore can be used as a positive control in an in vitro assay to compare the siRNA-knockdown cytotoxic effects of CD320 and LRP 2. In this latter assay, normal or cancer cells were transfected with siRNA sequences specifically targeting CD320 or LRP2, alone or in combination, or with control sirnas, similar to the experiments providing the data of figures 3, 4 and 5. In figures 3, 4 and 5, protein levels were measured, but in the in vitro assay, cell viability was measured.

Referring now to fig. 8, an overview of a functional assay for screening (ds) siRNA for effect on cell proliferation is shown. To quantify the effect of knockdown of CD320 and LRP2 on cell proliferation, cells were plated in 24-well plates. The next day, cells were transfected with sirnas against CD320 and/or LRP 2. For effective toxicity, cell lines may require repeated transfections and/or times (cell line dependent). In this experimental design, there is room for re-infection and some cell lines are required for effective toxicity. At the end of the study, cell growth of the cell lines was analyzed by CTG assay.

Referring now to FIG. 10B, MDA-MB-231 triple negative breast cancer cells were plated at 20,000 cells/well in 24-well plates. The following day, cells were transfected with an siRNA selected from OSC17, OSC47, OSL231 and OSL245 at 20 nM. Cells were also transfected with a combination of two sirnas, one targeting CD320 and the other LRP2, each at 10nM, where the CD320 targeting siRNA was selected from OSC17 and OSC47 and the LRP2 targeting siRNA was selected from OSL231 and OSL245, each administered at a dose of 10 nM. As indicated in table 9, the transfection of cells was repeated 4 times over the course of 11 days. On day 11, cells were analyzed for cell growth by CTG assay. The percent cell survival compared to the non-targeted control (OSS2) is shown. Data shown are mean-/+ SEM of 6 experiments.

Referring now to FIG. 11, MDA-MB-231 and DU-145 cells were transfected with 20nM negative control siRNA (OSS2), 20nM siRNA targeting CD320 (OSC17) or 20nM siRNA targeting LRP2 (OSL 245). Cells were also transfected with a combination of CD320 targeting siRNA (OSC17) and LRP2 targeting siRNA (OSL24), with sirnas in the concentration range of (2-20nM), so that the concentration of both sirnas was equal to 20nM of total transfected siRNA, as shown in figure 11. Cells were transfected repeatedly, and percent cell survival was shown, as shown in table 9.

Referring now to FIG. 12, MDA-MB-231 breast cancer cells were transfected with 20nM negative control siRNA (OSS2), 20nM siRNA targeting CD320 (OSC17) or 20nM siRNA targeting LRP2 (OSL 245). Lysates were prepared daily over 5 days. Immunoblotting was performed on lysates for CD320 protein level (fig. 12A) or LRP2 protein level (fig. 12B).

Referring now to fig. 9 and 10, data quantifying the effect of CD320 and LRP2 knockdown in various cell lines is shown. As indicated, representative cell lines of several cancer types or normal fibroblasts were transfected with sirnas against CD320 or LRP2, alone or in combination. For effective toxicity, cells were repeatedly transfected and then viability was determined by CTG assay, as listed in table 9. In our assay, doxorubicin-treated cells were used as a positive control for cytotoxicity.

The individual experimental data shown in fig. 9 and 10 and other cell lines we screened are summarized in table 9. These experiments show the broad applicability of siCD320 and silop 2 toxicity in a variety of cancer types.

Referring now to FIG. 13, a schematic of PEI and siRNA complexes is shown. PEI and siRNA were mixed together. Subsequently, the multimeric complex (nanoparticle, broadly) form of the PEI-siRNA complex can enter the cell via endocytosis or pinocytosis mechanisms.

Referring now to FIG. 14, siRNA are short RNA duplexes of typically 16 to 30 nucleotides; the sequence of the siRNA is complementary to mRNA expressed in the cell. Exogenous siRNA duplexes are introduced into cells by transfection. The siRNA duplex is unwound by the RISC (RNA-induced silencing complex) complex, whereby the guide strand of the siRNA hybridizes to its complementary mRNA molecule. mRNA is degraded by the RISC/AGO complex, and has an RNase cleavage activity. The end result is degradation of the mRNA targeted by the siRNA and no production of the protein encoded by the mRNA. This results in a "knock-down" effect or reduced protein levels of the gene targeted by the siRNA compared to control-treated cells.

Referring now to fig. 15, the effectiveness of interferrin in delivering siRNA to cancer cells is shown. The siRNA indicated at 2nM was transfected into A172 and MDA-MB-435S cells according to the manufacturer' S protocol. Cell lysates were prepared 3 days post infection and analyzed for CD320 protein levels by immunoblotting. OSS1 and OSS2 were non-targeted siRNA controls. In this experiment, two sequences were tested. Compared to OSS1, CD320 protein levels were knocked down to 9% to 18% for a172 cells and 26% to 48% for MDA-MB-435S cells. More effective knockdown of CD320 was observed when siRNA was delivered with other transfection reagents (e.g., RNAiMAX, Viromer Blue) used in experiments previously specifically described for MDA-MB-435S cells. The Polyplus interferrin platform has been tested in our laboratory in principle validation experiments in vitro, so that the platform is capable of delivering siRNA to target cells in vitro.

Referring now to fig. 16, treatment of breast, prostate and skin cancer cells with a CD320 receptor inhibitor or an LRP2 receptor inhibitor, or a combination of both, in an amount effective to inhibit cancer cell proliferation is shown compared to control cells treated with control siRNA. MDA-MB-231, DU145, LnCAP and MDA-MB-435S cells were plated at 20,000 cells per well in 24-well plates. The following day, cells were transfected with sirnas indicated at 20nM to knock down CD320, LRP2 or missense controls. For the combination of siRNAs, cells were treated with 10nM each siRNA (20nM total treatment). Cells were transfected repeatedly for the time lengths indicated in table 9, as in table 9. At the end of the experiment, photographs of the indicated cells were taken.

TABLE 9 summary of functional siRNA data screening

Note that: the values represent percent survival compared to the negative control OSS 2.

A murine human tumor xenograft model was established using triple negative breast cancer cells injected ventrally in nude mice (MDA-MB-231) to test the efficacy of combined dose administration of OSC17 and OSL 245. Drug administration is performed by repeated dose administration within a drug concentration range using intratumoral, iv, ip, or dedicated routes of administration. The dose administration schedule is based on pilot studies (pilot studios) to determine the tolerability of the delivery vehicle and drug and will be incorporated within the scope of the teachings in the art. Delivery platforms are nanoparticles, liposomes, micelles, polymers, small molecule conjugates, aptamers, and antibody conjugates. Compounding techniques containing the elements of the delivery systems described above are also known.

The production method consists of the synthesis of two single-stranded oligonucleotides of a double helix by conventional solid-phase oligonucleotide synthesis. After purification, the two oligonucleotides were annealed into a double helix.

In vivoIs a cationic polymer delivery system that binds negatively charged siRNA molecules to a cationic polyamine polymer. The use of both ip and intratumoral has been reported in xenograft models using MCF-7 (mammary gland), MDA-MB-231 (mammary gland) and A549 (lung) cell lines. This delivery system is currently used in 7 human clinical trials (table 10). Formulated siRNA are reported to be very stable.

TABLE 10 in vivo-Clinical trial use of

Note that in the specification and claims, "about" or "approximately" means within twenty percent (20%) of the recited numerical amount. Although the invention has been described in detail with particular reference to these embodiments, other embodiments can achieve the same results. For example, an antisense oligonucleotide complementary to a target mRNA may inhibit expression of a protein of interest, although the antisense oligonucleotide is not provided as dsRNA and may not bind to the RISC/AGO complex. Alterations and modifications of the invention will be obvious to those skilled in the art, and it is intended to cover in the appended claims all such modifications and equivalents. The entire disclosures of all references, patent applications, patents, and patent publications cited above are hereby incorporated by reference.

Sequence listing

<110> BIOAFFINITY TECHNOLOGIES, INC.

<120> compositions and methods for treating cancer

<130> 32064-1035-PCT

<140>

<141>

<150> 62/785,315

<151> 2018-12-27

<160> 956

<170> PatentIn version 3.5

<210> 1

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 1

ucuuaucccu gcgcacgcgc att 23

<210> 2

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 2

ucucuuaucc cugcgcacgc gtt 23

<210> 3

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 3

augcuguccc cacagcggcg ctt 23

<210> 4

<211> 23

<212> DNA

<213> Artificial sequence

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<223> description of artificial sequences: synthesis of

Oligonucleotides

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Oligonucleotides

<400> 4

auccaaccgc cgcucaugcu gtt 23

<210> 5

<211> 23

<212> DNA

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Oligonucleotides

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Oligonucleotides

<400> 5

uggaaagcgg gcucgcggcg gtt 23

<210> 6

<211> 23

<212> DNA

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Oligonucleotides

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Oligonucleotides

<400> 6

aacuuggugg gugggcacga gtt 23

<210> 7

<211> 23

<212> DNA

<213> Artificial sequence

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Oligonucleotides

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Oligonucleotides

<400> 7

uggaacuugg ugggugggca ctt 23

<210> 8

<211> 23

<212> DNA

<213> Artificial sequence

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Oligonucleotides

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Oligonucleotides

<400> 8

acuggaacuu gguggguggg ctt 23

<210> 9

<211> 23

<212> DNA

<213> Artificial sequence

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<223> description of artificial sequences: synthesis of

Oligonucleotides

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Oligonucleotides

<400> 9

uaagccacug gugcggcacu gtt 23

<210> 10

<211> 23

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<213> Artificial sequence

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Oligonucleotides

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Oligonucleotides

<400> 10

acgcauaagc cacuggugcg gtt 23

<210> 11

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

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Oligonucleotides

<400> 11

uccaaguccc ugucgcagcg ctt 23

<210> 12

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

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Oligonucleotides

<400> 12

uccucaucgc ugccaucgcu gtt 23

<210> 13

<211> 23

<212> DNA

<213> Artificial sequence

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Oligonucleotides

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Oligonucleotides

<400> 13

ucacugacgc cggugcaggg gtt 23

<210> 14

<211> 23

<212> DNA

<213> Artificial sequence

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<223> description of artificial sequences: synthesis of

Oligonucleotides

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<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 14

uugucaguuc ccccagagca gtt 23

<210> 15

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

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Oligonucleotides

<400> 15

uucuugucag uucccccaga gtt 23

<210> 16

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 16

aguuucuugu caguuccccc att 23

<210> 17

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 17

caguugcgca guuucuuguc aguuctt 27

<210> 18

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

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Oligonucleotides

<400> 18

caguugcgca guuucuuguc aguuctt 27

<210> 19

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

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Oligonucleotides

<400> 19

caguugcgca guuucuuguc aguuctt 27

<210> 20

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 20

caguugcgca guuucuuguc aguuctt 27

<210> 21

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 21

caguugcgca guuucuuguc aguuc 25

<210> 22

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 22

caguugcgca guuucuuguc aguuc 25

<210> 23

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 23

caguugcgca guuucuuguc aguuctt 27

<210> 24

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 24

caguugcgca guuucuuguc aguuctt 27

<210> 25

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 25

caguugcgca guuucuuguc aguuc 25

<210> 26

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 26

caguugcgca guuucuuguc aguuctt 27

<210> 27

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 27

caguugcgca guuucuuguc aguuc 25

<210> 28

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 28

caguugcgca guuucuuguc aguuctt 27

<210> 29

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 29

caguugcgca guuucuuguc aguuc 25

<210> 30

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 30

caguugcgca guuucuuguc aguuctt 27

<210> 31

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 31

caguugcgca guuucuuguc aguuctt 27

<210> 32

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 32

caguugcgca guuucuuguc aguuctt 27

<210> 33

<211> 23

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 33

caguugcgca guuucuuguc agu 23

<210> 34

<211> 23

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 34

caguugcgca guuucuuguc agu 23

<210> 35

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 35

augcagucau cgcucagcgu gtt 23

<210> 36

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 36

aaugcaguca ucgcucagcg utt 23

<210> 37

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 37

uggaaugcag ucaucgcuca gtt 23

<210> 38

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 38

aguggaaugc agucaucgcu ctt 23

<210> 39

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 39

acagucuggg uggccgucgc att 23

<210> 40

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 40

auugguucca cagccgagcu ctt 23

<210> 41

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 41

ucucauuggu uccacagccg att 23

<210> 42

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 42

aucucauugg uuccacagcc gtt 23

<210> 43

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 43

aggaucucau ugguuccaca gtt 23

<210> 44

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 44

ugagagaggu gacacucucc att 23

<210> 45

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 45

ugguuguggc auuccugaga gtt 23

<210> 46

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 46

uggcauuccc gacagagggg att 23

<210> 47

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 47

aggauguggc auucccgaca gtt 23

<210> 48

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 48

uuccagacug gucuccggca gtt 23

<210> 49

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 49

auaaccccau aggcaguugg gtt 23

<210> 50

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 50

uugcacugag caccgcagca gtt 23

<210> 51

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 51

aaaaggagga ggguggcggu gtt 23

<210> 52

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 52

acaaaaggag gaggguggcg gtt 23

<210> 53

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 53

accaguaacc ccagugggcg gtt 23

<210> 54

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 54

uucauggcca ccaguaaccc ctt 23

<210> 55

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 55

acuccuucau ggccaccagu att 23

<210> 56

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 56

uucugacagc agcagggacu ctt 23

<210> 57

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 57

ucuguucuga cagcagcagg gtt 23

<210> 58

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 58

ucuucuguuc ugacagcagc att 23

<210> 59

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 59

aggucuucug uucugacagc att 23

<210> 60

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 60

uuguccucag ggcagcgagg utt 23

<210> 61

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 61

aagugcuugu ccucagggca gtt 23

<210> 62

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 62

uacccauccg caucacugcu ctt 23

<210> 63

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 63

ucucugaggg cuggugugcc ctt 23

<210> 64

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 64

aagagcucag gucucugagg gtt 23

<210> 65

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 65

aagagcucag gucucugagg gtt 23

<210> 66

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 66

aagagcucag gucucugagg gtt 23

<210> 67

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 67

aagagcucag gucucugagg gtt 23

<210> 68

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 68

aagagcucag gucucugagg g 21

<210> 69

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 69

aagagcucag gucucugagg g 21

<210> 70

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 70

aagagcucag gucucugagg gtt 23

<210> 71

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 71

aagagcucag gucucugagg gtt 23

<210> 72

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 72

aagagcucag gucucugagg g 21

<210> 73

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 73

aagagcucag gucucugagg gtt 23

<210> 74

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 74

aagagcucag gucucugagg g 21

<210> 75

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 75

aagagcucag gucucugagg gtt 23

<210> 76

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 76

aagagcucag gucucugagg g 21

<210> 77

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 77

aagagcucag gucucugagg g 21

<210> 78

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 78

aagagcucag gucucugagg gtt 23

<210> 79

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 79

aagagcucag gucucugagg gtt 23

<210> 80

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 80

aagagcucag gucucugagg gtt 23

<210> 81

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 81

aagagcucag gucucugagg g 21

<210> 82

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 82

aagagcucag gucucugagg gtt 23

<210> 83

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 83

agaagagcuc aggucucuga gtt 23

<210> 84

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 84

auagggagug uccagggacc ctt 23

<210> 85

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 85

uccauaggga guguccaggg att 23

<210> 86

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 86

aucuccauag ggagugucca gtt 23

<210> 87

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 87

ucaguucugg cuguggcagg utt 23

<210> 88

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 88

uucuaccccc ugggagcugc ctt 23

<210> 89

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 89

aagcacaggg ccguucuacc ctt 23

<210> 90

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 90

ugucuuaagc acagggccgu utt 23

<210> 91

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 91

agugucuuaa gcacagggcc gtt 23

<210> 92

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 92

uuuuuugagg augugaagca att 23

<210> 93

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 93

uuuuuuugag gaugugaagc att 23

<210> 94

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 94

agagaauagg gacgcgugcg ctt 23

<210> 95

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 95

cgagagaaua gggacgcgug ctt 23

<210> 96

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 96

aguacgacag gggugucgcc gtt 23

<210> 97

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 97

gguagguugg cggcgaguac gtt 23

<210> 98

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 98

ccaccuuucg cccgagcgcc gtt 23

<210> 99

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 99

ccuugaacca cccacccgug ctt 23

<210> 100

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 100

ugaccuugaa ccacccaccc gtt 23

<210> 101

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 101

cgugaccuug aaccacccac ctt 23

<210> 102

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 102

guauucggug accacgccgu gtt 23

<210> 103

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 103

cgugcguauu cggugaccac gtt 23

<210> 104

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 104

ucagguucag ggacagcguc gtt 23

<210> 105

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 105

ggaggaguag cgacgguagc gtt 23

<210> 106

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 106

ucagugacug cggccacguc ctt 23

<210> 107

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 107

agaacaguca agggggucuc gtt 23

<210> 108

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 108

caaagaacag ucaagggggu ctt 23

<210> 109

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 109

cgucaaagaa cagucaaggg gtt 23

<210> 110

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 110

gaacugacaa gaaacugcgc aacugtt 27

<210> 111

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 111

gaacugacaa gaaacugcgc aacugtt 27

<210> 112

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 112

gaacugacaa gaaacugcgc aacugtt 27

<210> 113

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 113

gaacugacaa gaaacugcgc aacug 25

<210> 114

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 114

gaacugacaa gaaacugcgc aacugtt 27

<210> 115

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 115

gaacugacaa gaaacugcgc aacug 25

<210> 116

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 116

gaacugacaa gaaacugcgc aacugtt 27

<210> 117

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 117

gaacugacaa gaaacugcgc aacugtt 27

<210> 118

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 118

gaacugacaa gaaacugcgc aacugtt 27

<210> 119

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 119

gaacugacaa gaaacugcgc aacug 25

<210> 120

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 120

gaacugacaa gaaacugcgc aacug 25

<210> 121

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 121

gaacugacaa gaaacugcgc aacugtt 27

<210> 122

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 122

gaacugacaa gaaacugcgc aacug 25

<210> 123

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 123

ugacaagaaa cugcgcaacu gtt 23

<210> 124

<211> 17

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 124

gaaacugcgc aacugtt 17

<210> 125

<211> 17

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 125

gaaacugcgc aacugtt 17

<210> 126

<211> 15

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 126

gaaacugcgc aacug 15

<210> 127

<211> 15

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 127

gaaacugcgc aacug 15

<210> 128

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 128

cuuacgucag uagcgagucg ctt 23

<210> 129

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 129

ccuuacguca guagcgaguc gtt 23

<210> 130

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 130

ucaccuuacg ucaguagcga gtt 23

<210> 131

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 131

acucaccuua cgucaguagc gtt 23

<210> 132

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 132

ccugucagac ccaccggcag ctt 23

<210> 133

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 133

aguaaccaag gugucggcuc gtt 23

<210> 134

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 134

cuagaguaac caaggugucg gtt 23

<210> 135

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 135

ccuagaguaa ccaagguguc gtt 23

<210> 136

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 136

ccuccuagag uaaccaaggu gtt 23

<210> 137

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 137

ggacucucuc cacugugaga gtt 23

<210> 138

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 138

guaccaacac cguaaggacu ctt 23

<210> 139

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 139

acaccguaag ggcugucucc ctt 23

<210> 140

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 140

ccuccuacac cguaagggcu gtt 23

<210> 141

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 141

cgaaggucug accagaggcc gtt 23

<210> 142

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 142

guuauugggg uauccgucaa ctt 23

<210> 143

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 143

cgaacgugac ucguggcguc gtt 23

<210> 144

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 144

uguuuuccuc cucccaccgc ctt 23

<210> 145

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 145

ccuguuuucc uccucccacc gtt 23

<210> 146

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 146

gguggucauu ggggucaccc gtt 23

<210> 147

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 147

ggaaguaccg guggucauug gtt 23

<210> 148

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 148

ccugaggaag uaccgguggu ctt 23

<210> 149

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 149

acaagacugu cgucgucccu gtt 23

<210> 150

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 150

gaagacaaga cugucgucgu ctt 23

<210> 151

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 151

ccagaagaca agacugucgu ctt 23

<210> 152

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 152

gcuccagaag acaagacugu ctt 23

<210> 153

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 153

cgaacaggag ucccgucgcu ctt 23

<210> 154

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 154

cguucacgaa caggaguccc gtt 23

<210> 155

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 155

ccauggguag gcguagugac gtt 23

<210> 156

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 156

ccagagacuc ccgaccacac gtt 23

<210> 157

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 157

cccucagaga ccugagcucu utt 23

<210> 158

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 158

cccucagaga ccugagcucu utt 23

<210> 159

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 159

cccucagaga ccugagcucu utt 23

<210> 160

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 160

cccucagaga ccugagcucu u 21

<210> 161

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 161

cccucagaga ccugagcucu utt 23

<210> 162

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 162

cccucagaga ccugagcucu u 21

<210> 163

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 163

cccucagaga ccugagcucu utt 23

<210> 164

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 164

cccucagaga ccugagcucu utt 23

<210> 165

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 165

cccucagaga ccugagcucu utt 23

<210> 166

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 166

cccucagaga ccugagcucu u 21

<210> 167

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 167

cccucagaga ccugagcucu u 21

<210> 168

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 168

cccucagaga ccugagcucu utt 23

<210> 169

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 169

cccucagaga ccugagcucu u 21

<210> 170

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 170

cccucagaga ccugagcucu utt 23

<210> 171

<211> 17

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 171

gagaccugag cucuutt 17

<210> 172

<211> 17

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 172

gagaccugag cucuutt 17

<210> 173

<211> 15

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 173

gagaccugag cucuu 15

<210> 174

<211> 15

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 174

gagaccugag cucuu 15

<210> 175

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 175

ucuucucgag uccagagacu ctt 23

<210> 176

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 176

ggucuucucg aguccagaga ctt 23

<210> 177

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 177

gguaucccuc acaggucccu gtt 23

<210> 178

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 178

agagguaucc cucacagguc ctt 23

<210> 179

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 179

ccuagaggua ucccucacag gtt 23

<210> 180

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 180

ggagucaaga ccgacaccgu ctt 23

<210> 181

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 181

gcaagauggg ggacccucga ctt 23

<210> 182

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 182

aauucguguc ccggcaagau gtt 23

<210> 183

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 183

ucacagaauu cgugucccgg ctt 23

<210> 184

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 184

ccucacagaa uucguguccc gtt 23

<210> 185

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 185

aaaaaaaacu ccuacacuuc gtt 23

<210> 186

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 186

aaaaaaaaac uccuacacuu ctt 23

<210> 187

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 187

uacuuuguga gcaaucuuga ctt 23

<210> 188

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 188

auucacuugg gauacacuga ctt 23

<210> 189

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 189

acaugaaaac ucauugugca att 23

<210> 190

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 190

ucuuuacagu caucuucucc att 23

<210> 191

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 191

uaucuuuaca gucaucuucu ctt 23

<210> 192

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 192

aacauuuaug aacaucauga gtt 23

<210> 193

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 193

ucacaaacuu uauaaaugga gtt 23

<210> 194

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 194

aucacaaacu uuauaaaugg att 23

<210> 195

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 195

auacuacagu auuuuccggu att 23

<210> 196

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 196

ucauacuaca guauuuuccg gtt 23

<210> 197

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 197

acaaauuccc cauaucuggc att 23

<210> 198

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 198

aagauauacc cuucuucaca gtt 23

<210> 199

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 199

uuagcuuugc aauacugucc att 23

<210> 200

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 200

aucauuagcu uugcaauacu gtt 23

<210> 201

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 201

aaaggaauca uuagcuuugc att 23

<210> 202

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 202

augaauauca ccaauuaaca att 23

<210> 203

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 203

aaaaaaccuu auuuugcacg gtt 23

<210> 204

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 204

ugaaaaaacc uuauuuugca ctt 23

<210> 205

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 205

aaugucaacu gaaaaaaccu utt 23

<210> 206

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 206

uaaugucaac ugaaaaaacc utt 23

<210> 207

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 207

uuaaaccauu aaugucaacu gtt 23

<210> 208

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 208

uauuuaaacc auuaauguca att 23

<210> 209

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 209

uagauuuuau uauuaaccca gtt 23

<210> 210

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 210

auagauuuua uuauuaaccc att 23

<210> 211

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 211

aaauuuacca uaucuaugcg gtt 23

<210> 212

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 212

aaguuuucag uuauaagggu att 23

<210> 213

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 213

aauaaauaac caacaguugg gtt 23

<210> 214

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 214

agaaaaauaa auaaccaaca gtt 23

<210> 215

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 215

auaucauauc cagaguuacc ctt 23

<210> 216

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 216

aguuucaaug uaaucaaacc gtt 23

<210> 217

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 217

uuacaguuuc aauguaauca att 23

<210> 218

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 218

auaaguuaca guuucaaugu att 23

<210> 219

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 219

ucuuuacacg gauugguagc att 23

<210> 220

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 220

aaaaucaauc ccgacaaaga att 23

<210> 221

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 221

ucugaaaaaa agauagugcu gtt 23

<210> 222

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 222

aucugaaaaa aagauagugc utt 23

<210> 223

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 223

aaaaaucaug uguuuugaca utt 23

<210> 224

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 224

uuugcuuaaa aaucaugugu utt 23

<210> 225

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 225

aacuuucaac auuuuccacc ctt 23

<210> 226

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 226

uugaaaucca aucaaaagcc att 23

<210> 227

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 227

uuugaaaucc aaucaaaagc ctt 23

<210> 228

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 228

uagagauucu uugaaaucca att 23

<210> 229

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 229

auagagauuc uuugaaaucc att 23

<210> 230

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 230

uuuaaauacu gaacuacugu gtt 23

<210> 231

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 231

uauuuaaaua cugaacuacu gtt 23

<210> 232

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 232

auagauaccc ggcaaaagga utt 23

<210> 233

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 233

aagaguagug uuuauuacag gtt 23

<210> 234

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 234

aucaaaauag gcaucuaccc att 23

<210> 235

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 235

ucaauuuuau caaaauaggc att 23

<210> 236

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 236

uaaaugcucu ccaaagaugg ctt 23

<210> 237

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 237

ucaaaugcag uauguaagca att 23

<210> 238

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 238

uucaaaugca guauguaagc att 23

<210> 239

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 239

ugauuacagg cguuagaacc att 23

<210> 240

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 240

uguuaucaug acaaucaucg att 23

<210> 241

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 241

uuaucacagg uguauugggu gtt 23

<210> 242

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 242

auuaucacag guguauuggg utt 23

<210> 243

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 243

aguucuuuga gauacacugg utt 23

<210> 244

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 244

ucgaauugca guucuuuuca utt 23

<210> 245

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 245

ucaauacauc gaugauuggg gtt 23

<210> 246

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 246

aacgauaggu caauacaucg att 23

<210> 247

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 247

acaaacgaua ggucaauaca utt 23

<210> 248

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 248

ucaaaaacac caucacaacg att 23

<210> 249

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 249

ucacauuccc agaaguucgg gtt 23

<210> 250

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 250

aucacauucc cagaaguucg gtt 23

<210> 251

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 251

ugaugaaggg caagucuugg gtt 23

<210> 252

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 252

agaaucauug gcaaguaaga att 23

<210> 253

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 253

uaucacauuc aucuaugucu utt 23

<210> 254

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 254

aauaucacau ucaucuaugu ctt 23

<210> 255

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 255

aacauguagc cuguaucaca ctt 23

<210> 256

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 256

ucacuuucua acauguagcc utt 23

<210> 257

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 257

aucacuuucu aacauguagc ctt 23

<210> 258

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 258

aauguaagaa ccauucucga ctt 23

<210> 259

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 259

uacaauguaa gaaccauucu ctt 23

<210> 260

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 260

aaaaucaaca gcuacaaugu att 23

<210> 261

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 261

auugaaucaa aaucaacagc utt 23

<210> 262

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 262

uaauugaauc aaaaucaaca gtt 23

<210> 263

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 263

aagauacgac cacuaauuga att 23

<210> 264

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 264

aguuucaguc aagaugaugc utt 23

<210> 265

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 265

aauaguuuca gucaagauga utt 23

<210> 266

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 266

uauugcaaua guuucaguca att 23

<210> 267

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 267

ucuauugcaa uaguuucagu ctt 23

<210> 268

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 268

aaucuauugc aauaguuuca gtt 23

<210> 269

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 269

auuuuggaga cuucaauugu utt 23

<210> 270

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 270

uuagguuuuu acuaaucagc att 23

<210> 271

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 271

ucauucuggg aucuaaugcu att 23

<210> 272

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 272

uucauucugg gaucuaaugc utt 23

<210> 273

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 273

aguagaugcu cauucauucu gtt 23

<210> 274

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 274

auuauaauca caaaagucca utt 23

<210> 275

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 275

uccauuauaa ucacaaaagu ctt 23

<210> 276

<211> 21

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 276

ugccguauaa ucaaaucact t 21

<210> 277

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 277

auauuauaca uuacaacuga ctt 23

<210> 278

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 278

auugaauauu auacauuaca att 23

<210> 279

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 279

aauuugguug uuucgaagga utt 23

<210> 280

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 280

acggaauuug guuguuucga att 23

<210> 281

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 281

uuacaguuau uaagaaaggu utt 23

<210> 282

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 282

uccaaaaauu auauguugcc utt 23

<210> 283

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 283

uuccaaaaau uauauguugc ctt 23

<210> 284

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 284

ucuaaaccau ucuguauccc utt 23

<210> 285

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 285

aucuaaacca uucuguaucc ctt 23

<210> 286

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 286

uucaacaucu aaaccauucu gtt 23

<210> 287

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 287

auuuucaacc caauagaugu att 23

<210> 288

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 288

uauagaagca aauacugucc utt 23

<210> 289

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 289

uagauauaga agcaaauacu gtt 23

<210> 290

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 290

uaaggccagg uucauagaag gtt 23

<210> 291

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 291

ucuugaaauc caaucuaagg ctt 23

<210> 292

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 292

auaaagguuu cuugaaaucc att 23

<210> 293

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 293

ucaaaaccuc gauugacuga gtt 23

<210> 294

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 294

uucuguaucu gauaucuccg utt 23

<210> 295

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 295

uuucuguauc ugauaucucc gtt 23

<210> 296

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 296

uuuuucugua ucugauaucu ctt 23

<210> 297

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 297

aucaauguuu uucuguaucu gtt 23

<210> 298

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 298

auaaaggaaa gaaucaugga ctt 23

<210> 299

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 299

aauaaaggaa agaaucaugg att 23

<210> 300

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 300

ucaguauaau aaaggaaaga att 23

<210> 301

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 301

uuucaaugac cucauacugu utt 23

<210> 302

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 302

auuuggaaca uuaucucuca att 23

<210> 303

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 303

agauuuggaa cauuaucucu ctt 23

<210> 304

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 304

ucagauuugg aacauuaucu ctt 23

<210> 305

<211> 21

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 305

uugcuacagc cauuugaggt t 21

<210> 306

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 306

augaaagagu uauauggaga gtt 23

<210> 307

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 307

acaaugaaag aguuauaugg att 23

<210> 308

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 308

ugaaacaaca augaaagagu utt 23

<210> 309

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 309

auugaaacaa caaugaaaga gtt 23

<210> 310

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 310

agcuaaagcc ucugauugca gtt 23

<210> 311

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 311

aagcuaaagc cucugauugc att 23

<210> 312

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 312

acaauuccaa gcuaaagccu ctt 23

<210> 313

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 313

ugacaauucc aagcuaaagc ctt 23

<210> 314

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 314

ugaaugaucu gacaauucca att 23

<210> 315

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 315

auguucauca gagaagaucc att 23

<210> 316

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 316

uauuccaugu gucacaaugu utt 23

<210> 317

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 317

acuucuauca guguuucaga att 23

<210> 318

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 318

uauugauccg cagaacuucu att 23

<210> 319

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 319

uguucuuggg aucuacaaca att 23

<210> 320

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 320

aaagaacgcu caaucuuugg utt 23

<210> 321

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 321

uaaacguagc caucacuucg gtt 23

<210> 322

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 322

aucuaaagaa ucaucaaccc att 23

<210> 323

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 323

uuauaucuaa agaaucauca att 23

<210> 324

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 324

auagaauuuu caaaaacagu gtt 23

<210> 325

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 325

ugauagaauu uucaaaaaca gtt 23

<210> 326

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 326

uuucaaauuc cuaucuaccc att 23

<210> 327

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 327

uuuucaaauu ccuaucuacc ctt 23

<210> 328

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 328

auauugucuc uuaucacugu gtt 23

<210> 329

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 329

ugauauuguc ucuuaucacu gtt 23

<210> 330

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 330

ugaaauggca caauucuugc ctt 23

<210> 331

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 331

uguugaaaug gcacaauucu utt 23

<210> 332

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 332

aauuuucugu ugaaauggca ctt 23

<210> 333

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 333

aaauuuucug uugaaauggc att 23

<210> 334

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 334

auuagacaag gcaaagauga gtt 23

<210> 335

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 335

acauuuauug uuuggaaagg utt 23

<210> 336

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 336

aucacuuaca cugucauagu ctt 23

<210> 337

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 337

uagauucuau cacuuacacu gtt 23

<210> 338

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 338

aguagauucu aucacuuaca ctt 23

<210> 339

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 339

uuuuguguga aguagauucu att 23

<210> 340

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 340

uaaauuuugu gugaaguaga utt 23

<210> 341

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 341

ucuaguaauc cagucaaagg ctt 23

<210> 342

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 342

aauucuucua guaauccagu ctt 23

<210> 343

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 343

uaaauucuuc uaguaaucca gtt 23

<210> 344

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 344

auaaauucuu cuaguaaucc att 23

<210> 345

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 345

auauacuggc cauagagagu ctt 23

<210> 346

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 346

uucuuugugu guacaaguca gtt 23

<210> 347

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 347

aauucuuugu guguacaagu ctt 23

<210> 348

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 348

ucgguaaauu cuuugugugu att 23

<210> 349

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 349

uguuacacug uuguuucugg utt 23

<210> 350

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 350

auuguuacac uguuguuucu gtt 23

<210> 351

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 351

aaacuguuca caaggauugu utt 23

<210> 352

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 352

acaucguuca ccauugucca ctt 23

<210> 353

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 353

uguuauugca cauaaacucc gtt 23

<210> 354

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 354

ucuguuauug cacauaaacu ctt 23

<210> 355

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 355

uuaugacauu uuguguaucc att 23

<210> 356

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 356

ugaauuauga cauuuugugu att 23

<210> 357

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 357

uuugaauuau gacauuuugu gtt 23

<210> 358

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 358

uacaaauauu ugaauuauga ctt 23

<210> 359

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 359

aaauaaacgc gaggaauaca att 23

<210> 360

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 360

aauaaguagg guuuucauca ctt 23

<210> 361

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 361

ucacaauacc aauguugagg att 23

<210> 362

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 362

uguuucuuga ucacaauacc att 23

<210> 363

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 363

aacaaucugu uucuugauca ctt 23

<210> 364

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 364

uuuacacaga gaaacucgga att 23

<210> 365

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 365

auuuacacag agaaacucgg att 23

<210> 366

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 366

uucugauucu caucguagcc gtt 23

<210> 367

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 367

auuuucagag caaguucucc utt 23

<210> 368

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 368

auaucuuugg gauacacagu ctt 23

<210> 369

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 369

agguaaacug auucuguugg ctt 23

<210> 370

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 370

auagaaacug guuaaggugu ctt 23

<210> 371

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 371

acaauagaaa cugguuaagg utt 23

<210> 372

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 372

ucaucaauau caacacaagu ctt 23

<210> 373

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 373

agauguagga gccuauuaca utt 23

<210> 374

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 374

ucgauguuac uguuuugccg gtt 23

<210> 375

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 375

uugcuaaaaa ugagauaggg utt 23

<210> 376

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 376

auuucucaaa uaguaacggu utt 23

<210> 377

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 377

aauuucucaa auaguaacgg utt 23

<210> 378

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 378

aaauuucuca aauaguaacg gtt 23

<210> 379

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 379

aguuaaauuu cucaaauagu att 23

<210> 380

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 380

aucuauaguu aaauuucuca att 23

<210> 381

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 381

uaaaaauagc caucuauagu utt 23

<210> 382

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 382

aucuaaugcc acaacauugu ctt 23

<210> 383

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 383

aauccaauac aaucucuucu ctt 23

<210> 384

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 384

acauucucuc aaugacuugc ctt 23

<210> 385

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 385

augauugucu ccuuguuugu ctt 23

<210> 386

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 386

auuaucacag acuuguuggu utt 23

<210> 387

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 387

uucaaaaaug guaauagcga att 23

<210> 388

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 388

ucuucaaaaa ugguaauagc gtt 23

<210> 389

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 389

auuuguuucc cuuuuccacu gtt 23

<210> 390

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 390

auuugaucca ucauauuugu utt 23

<210> 391

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 391

uauauggaug guacacaugg att 23

<210> 392

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 392

aaagaagacg gucuucauca gtt 23

<210> 393

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 393

ugaauucugu gaaguuguca ctt 23

<210> 394

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 394

acaaugucca cuuguacacu gtt 23

<210> 395

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 395

acacaauguc cacuuguaca ctt 23

<210> 396

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 396

uuuuugcauu cgaacauagu att 23

<210> 397

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 397

augguuuuug cauucgaaca utt 23

<210> 398

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 398

auacaaacau gguuuuugca utt 23

<210> 399

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 399

aucacauuuc caauauggcg gtt 23

<210> 400

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 400

ugaaguucuu caucugaacc att 23

<210> 401

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 401

auaaaugcag cgauuguugu ctt 23

<210> 402

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 402

auucuguaca agguuuaggg gtt 23

<210> 403

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 403

uauucuguac aagguuuagg gtt 23

<210> 404

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 404

auucauauuc uguacaaggu utt 23

<210> 405

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 405

uauucauauu cuguacaagg utt 23

<210> 406

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 406

uuauauucau auucuguaca att 23

<210> 407

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 407

uauugcaacc caguucaucg gtt 23

<210> 408

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 408

auauuuucag cacauguucu utt 23

<210> 409

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 409

uuaauugggu acaauuuugc utt 23

<210> 410

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 410

aaaaacauug guuucgaacc ctt 23

<210> 411

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 411

ugucaaaaac auugguuucg att 23

<210> 412

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 412

uucgaauucg gacauuguca gtt 23

<210> 413

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 413

auuauauuuu cgaauucgga ctt 23

<210> 414

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 414

agauuauauu uucgaauucg gtt 23

<210> 415

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 415

ucaucuugaa gauacucuga gtt 23

<210> 416

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 416

uauauuccuc aucuugaaga utt 23

<210> 417

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 417

uuugauagca ccaaaccuag agccctt 27

<210> 418

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 418

uuugauagca ccaaaccuag agccctt 27

<210> 419

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 419

uuugauagca ccaaaccuag agccctt 27

<210> 420

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 420

uuugauagca ccaaaccuag agccctt 27

<210> 421

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 421

uuugauagca ccaaaccuag agccc 25

<210> 422

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 422

uuugauagca ccaaaccuag agccc 25

<210> 423

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 423

uuugauagca ccaaaccuag agccctt 27

<210> 424

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 424

uuugauagca ccaaaccuag agccctt 27

<210> 425

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 425

uuugauagca ccaaaccuag agccc 25

<210> 426

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 426

uuugauagca ccaaaccuag agccctt 27

<210> 427

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 427

uuugauagca ccaaaccuag acccc 25

<210> 428

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 428

uuugauagca ccaaaccuag agccctt 27

<210> 429

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 429

uaucaaaccu cgauagcaac accgc 25

<210> 430

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 430

uuugauagca ccaaaccuag agccctt 27

<210> 431

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 431

uuugauagca ccaaaccuag agccctt 27

<210> 432

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 432

uuugauagca ccaaaccuag agccctt 27

<210> 433

<211> 23

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 433

uuugauagca ccaaaccuag agc 23

<210> 434

<211> 23

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 434

uuugauagca ccaaaccuag agc 23

<210> 435

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 435

ucaaaguugg ggauguaggc att 23

<210> 436

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 436

ucaguuucag gucaacuucc utt 23

<210> 437

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 437

uacguauuuc aguuucaggu ctt 23

<210> 438

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 438

uuacguauuu caguuucagg utt 23

<210> 439

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 439

aguuuagcca ccucaaugcg utt 23

<210> 440

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 440

aacauaagcc cuaguuuggg att 23

<210> 441

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 441

ucgauuuuag guuccuuucc ctt 23

<210> 442

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 442

ucgaaaacca ggauguugcg gtt 23

<210> 443

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 443

ucaaauaauc gauagaaagg ctt 23

<210> 444

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 444

uuguucaaau aaucgauaga att 23

<210> 445

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 445

uuaugguuuc aauaacgucc utt 23

<210> 446

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 446

uuuuaugguu ucaauaacgu ctt 23

<210> 447

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 447

auuuuauggu uucaauaacg utt 23

<210> 448

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 448

uuugcaauga cucuccuauc agucctt 27

<210> 449

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 449

uuugcaauga cucuccuauc agucctt 27

<210> 450

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 450

uuugcaauga cucuccuauc agucctt 27

<210> 451

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 451

uuugcaauga cucuccuauc agucctt 27

<210> 452

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 452

uuugcaauga cucuccuauc agucc 25

<210> 453

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 453

uuugcaauga cucuccuauc agucc 25

<210> 454

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 454

uuugcaauga cucuccuauc agucctt 27

<210> 455

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 455

uuugcaauga cucuccuauc agucctt 27

<210> 456

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 456

uuugcaauga cucuccuauc agucc 25

<210> 457

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 457

uuugcaauga cucuccuauc agucctt 27

<210> 458

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 458

uuugcaauga cucuccuauc acucc 25

<210> 459

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 459

uuugcaauga cucuccuauc agucctt 27

<210> 460

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 460

uauccuaagu cacacguuug acugc 25

<210> 461

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 461

uuugcaauga cucuccuauc agucctt 27

<210> 462

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 462

uuugcaauga cucuccuauc agucctt 27

<210> 463

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 463

uuugcaauga cucuccuauc agucctt 27

<210> 464

<211> 23

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 464

uuugcaauga cucuccuauc agu 23

<210> 465

<211> 23

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 465

uuugcaauga cucuccuauc agu 23

<210> 466

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 466

uagauaucca guauaacugg utt 23

<210> 467

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 467

uuuuguuucc auacuucucc ctt 23

<210> 468

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 468

auuuauuuug uuuccauacu utt 23

<210> 469

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 469

uauuguaucu gaguugauga att 23

<210> 470

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 470

ucaaaauagc aauuuccucc gtt 23

<210> 471

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 471

ucaucaaaau agcaauuucc utt 23

<210> 472

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 472

auuucacaau auuuuccggu gtt 23

<210> 473

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 473

uuugaaaacg ccauuucaca att 23

<210> 474

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 474

uucuauagug gaagaauccu gtt 23

<210> 475

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 475

auauccaugu uaagaucugc ctt 23

<210> 476

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 476

acaaagucuu cacucauugc ctt 23

<210> 477

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 477

uuauuaucca cauuuucaga utt 23

<210> 478

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 478

ucuuauuauc cacauuuuca gtt 23

<210> 479

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 479

uccauaauuc uuauuaucca ctt 23

<210> 480

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 480

uuccauaauu cuuauuaucc att 23

<210> 481

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 481

uuuucguuug aagagauucc att 23

<210> 482

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 482

uagauuuucg uuugaagaga utt 23

<210> 483

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 483

uuuagauuuu cguuugaaga gtt 23

<210> 484

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 484

uuguuuagau uuucguuuga att 23

<210> 485

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 485

uaguuuguuu agauuuucgu utt 23

<210> 486

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 486

uuucaaaguu gguaguuugu utt 23

<210> 487

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 487

auuggauuuu caaaguuggu att 23

<210> 488

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 488

auagauugga uuuucaaagu utt 23

<210> 489

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 489

uuaaaagugu cuucuguugc att 23

<210> 490

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 490

ucuuuaacaa gauuugcggu gtt 23

<210> 491

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 491

ucuucuuuaa caagauuugc gtt 23

<210> 492

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 492

ugguauagcu auacuucaga gtt 23

<210> 493

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 493

auuauucccu aaauagcugg utt 23

<210> 494

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 494

uaauuauucc cuaaauagcu gtt 23

<210> 495

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 495

auauaugugc aaaagugugu utt 23

<210> 496

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 496

aaauauaugu gcaaaagugu gtt 23

<210> 497

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 497

aacuuuuuuc aucuguuugu att 23

<210> 498

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 498

uaaaguacug aauguuaacu utt 23

<210> 499

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 499

uuuuuuucau aaaguacuga att 23

<210> 500

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 500

uauuuuuuuc auaaaguacu gtt 23

<210> 501

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 501

auuuguaaaa auaugagacg gtt 23

<210> 502

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 502

acauugugau aauuauuugu att 23

<210> 503

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 503

auacauauag uacauuguga utt 23

<210> 504

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 504

auauacauau aguacauugu gtt 23

<210> 505

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 505

aaagauauac auauaguaca utt 23

<210> 506

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 506

auuaccuuca gacaacuuca gtt 23

<210> 507

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 507

uauuuauagu auuaccuuca gtt 23

<210> 508

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 508

uaaucuuucc aaaauuuaca att 23

<210> 509

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 509

aguaacagga uaaucuuucc att 23

<210> 510

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 510

auucaguaac aggauaaucu utt 23

<210> 511

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 511

uagcaaauuc aguaacagga utt 23

<210> 512

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 512

uuagcaaauu caguaacagg att 23

<210> 513

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 513

ucuuuauuag caaauucagu att 23

<210> 514

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 514

aucauuuacu auaaugauca ctt 23

<210> 515

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 515

uucuuguugg aucauuuacu att 23

<210> 516

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 516

ucaauuccuu uucuuguugg att 23

<210> 517

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 517

auuuuauagg aaauaugagu gtt 23

<210> 518

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 518

uaauuuuaua ggaaauauga gtt 23

<210> 519

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 519

ugcuaaugug uaaaaaugga ctt 23

<210> 520

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 520

uugaacauua auuaagugcu att 23

<210> 521

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 521

auugaacauu aauuaagugc utt 23

<210> 522

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 522

auauugaaca uuaauuaagu gtt 23

<210> 523

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 523

aaauugacau guaauauuga att 23

<210> 524

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 524

aucaacauag ccauuaauca att 23

<210> 525

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 525

ucuauacaac acauaguggc ctt 23

<210> 526

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 526

augucuauac aacacauagu gtt 23

<210> 527

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 527

acugaauugc uuuuccuacc utt 23

<210> 528

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 528

aaauaaaaau guugucuugg ctt 23

<210> 529

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 529

aucacaaaua aaaauguugu ctt 23

<210> 530

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 530

aaugauaugg gauuuccuca utt 23

<210> 531

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 531

auuaaccaca aacucaaugc att 23

<210> 532

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 532

uuuaauuaac cacaaacuca att 23

<210> 533

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 533

uuugguuuca gaaauucagc utt 23

<210> 534

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 534

uuaugaagac acagauuugg utt 23

<210> 535

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 535

uuucauagaa acaaaaaccc att 23

<210> 536

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 536

augauauuuu cauagaaaca att 23

<210> 537

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 537

uauaaugaua uuuucauaga att 23

<210> 538

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 538

ugauuauaau gauauuuuca utt 23

<210> 539

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 539

auaaauagug auuauaauga utt 23

<210> 540

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 540

aaaagcuuaa uaagaauggu utt 23

<210> 541

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 541

aaaaagcuua auaagaaugg utt 23

<210> 542

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 542

uaaauguaca cauuuagcca ctt 23

<210> 543

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 543

auaaauguac acauuuagcc att 23

<210> 544

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 544

uauaaaugua cacauuuagc ctt 23

<210> 545

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 545

uucuaauaua aauguacaca utt 23

<210> 546

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 546

aagaauuaaa gaaaagaucu gtt 23

<210> 547

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 547

aauaagaauu aaagaaaaga utt 23

<210> 548

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 548

aaaccaauaa gaauuaaaga att 23

<210> 549

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 549

acuauaccca cuauuuaaga gtt 23

<210> 550

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 550

acaaaugugc aauauuagca ctt 23

<210> 551

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 551

aacaaaugug caauauuagc att 23

<210> 552

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 552

auguuucauu cauucaucca utt 23

<210> 553

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 553

aguaguauau guuucauuca utt 23

<210> 554

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 554

aaucaguagu auauguuuca utt 23

<210> 555

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 555

aaauaaucag uaguauaugu utt 23

<210> 556

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 556

aaucaaagua auuacaguca gtt 23

<210> 557

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 557

aucuaaucaa aguaauuaca gtt 23

<210> 558

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 558

uuauuuccag uuguuuaucu att 23

<210> 559

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 559

uuauuagaac uuuuucagca gtt 23

<210> 560

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 560

uuuauuagaa cuuuuucagc att 23

<210> 561

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 561

acaugaaaca cucguuagaa ctt 23

<210> 562

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 562

cauaagugaa cccuauguga ctt 23

<210> 563

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 563

gguguacuuu ugaguaacac gtt 23

<210> 564

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 564

auagaaaugu caguagaaga gtt 23

<210> 565

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 565

uaauagaaau gucaguagaa gtt 23

<210> 566

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 566

ccuuguaaau acuuguagua ctt 23

<210> 567

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 567

guaguguuug aaauauuuac ctt 23

<210> 568

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 568

gguaguguuu gaaauauuua ctt 23

<210> 569

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 569

aguaugaugu cauaaaaggc ctt 23

<210> 570

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 570

ucaguaugau gucauaaaag gtt 23

<210> 571

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 571

aguguuuaag ggguauagac ctt 23

<210> 572

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 572

gguucuauau gggaagaagu gtt 23

<210> 573

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 573

guaaucgaaa cguuaugaca gtt 23

<210> 574

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 574

cuuaguaauc gaaacguuau gtt 23

<210> 575

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 575

gguuuccuua guaaucgaaa ctt 23

<210> 576

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 576

gguacuuaua gugguuaauu gtt 23

<210> 577

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 577

acuuuuuugg aauaaaacgu gtt 23

<210> 578

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 578

ugacuuuuuu ggaauaaaac gtt 23

<210> 579

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 579

aauuacaguu gacuuuuuug gtt 23

<210> 580

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 580

uaauuacagu ugacuuuuuu gtt 23

<210> 581

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 581

uaaauuuggu aauuacaguu gtt 23

<210> 582

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 582

cuauaaauuu gguaauuaca gtt 23

<210> 583

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 583

cuaucuaaaa uaauaauugg gtt 23

<210> 584

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 584

ucuaucuaaa auaauaauug gtt 23

<210> 585

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 585

gguuuaaaug guauagauac gtt 23

<210> 586

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 586

gguucaaaag ucaauauucc ctt 23

<210> 587

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 587

uuuuauuuau ugguugucaa ctt 23

<210> 588

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 588

acucuuuuua uuuauugguu gtt 23

<210> 589

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 589

gcuauaguau aggucucaau gtt 23

<210> 590

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 590

ugucaaaguu acauuaguuu gtt 23

<210> 591

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 591

ucaaugucaa aguuacauua gtt 23

<210> 592

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 592

aguauucaau gucaaaguua ctt 23

<210> 593

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 593

auagaaaugu gccuaaccau ctt 23

<210> 594

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 594

aguuuuaguu agggcuguuu ctt 23

<210> 595

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 595

auagacuuuu uuucuaucac gtt 23

<210> 596

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 596

uauagacuuu uuuucuauca ctt 23

<210> 597

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 597

aauuuuuagu acacaaaacu gtt 23

<210> 598

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 598

gaaaacgaau uuuuaguaca ctt 23

<210> 599

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 599

guuugaaagu uguaaaaggu gtt 23

<210> 600

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 600

gaaacuuuag guuaguuuuc gtt 23

<210> 601

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 601

agaaacuuua gguuaguuuu ctt 23

<210> 602

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 602

uuaucucuaa gaaacuuuag gtt 23

<210> 603

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 603

guuaucucua agaaacuuua gtt 23

<210> 604

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 604

auaaauuuau gacuugauga ctt 23

<210> 605

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 605

caauaaauuu augacuugau gtt 23

<210> 606

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 606

cuuaucuaug ggccguuuuc ctt 23

<210> 607

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 607

uucucaucac aaauaauguc ctt 23

<210> 608

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 608

aauaguuuua uccguagaug gtt 23

<210> 609

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 609

cgaguuaaaa uaguuuuauc ctt 23

<210> 610

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 610

uuauuuacga gagguuucua ctt 23

<210> 611

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 611

aaaguuuacg ucauacauuc gtt 23

<210> 612

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 612

uaaaguuuac gucauacauu ctt 23

<210> 613

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 613

caacuaaugu ccgcaaucuu gtt 23

<210> 614

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 614

ugacaauagu acuguuagua gtt 23

<210> 615

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 615

cuaauagugu ccacauaacc ctt 23

<210> 616

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 616

acuaauagug uccacauaac ctt 23

<210> 617

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 617

ggucaagaaa cucuauguga ctt 23

<210> 618

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 618

acagcuuaac gucaagaaaa gtt 23

<210> 619

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 619

ccaguuaugu agcuacuaac ctt 23

<210> 620

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 620

guuugcuauc caguuaugua gtt 23

<210> 621

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 621

ucuguuugcu auccaguuau gtt 23

<210> 622

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 622

uuaguuuuug ugguaguguu gtt 23

<210> 623

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 623

guaguguaag ggucuucaag ctt 23

<210> 624

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 624

gguaguguaa gggucuucaa gtt 23

<210> 625

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 625

auacuacuuc ccguucagaa ctt 23

<210> 626

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 626

aaucuuagua accguucauu ctt 23

<210> 627

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 627

uuauagugua aguagauaca gtt 23

<210> 628

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 628

ucuuauagug uaaguagaua ctt 23

<210> 629

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 629

gauuguacau cggacauagu gtt 23

<210> 630

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 630

guagugaaag auuguacauc gtt 23

<210> 631

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 631

gguagugaaa gauuguacau ctt 23

<210> 632

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 632

uguuacauuc uugguaagag ctt 23

<210> 633

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 633

cgauguuaca uucuugguaa gtt 23

<210> 634

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 634

aguuuuaguu gucgauguua ctt 23

<210> 635

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 635

auuaacuuag uuuuaguugu ctt 23

<210> 636

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 636

ugauuaacuu aguuuuaguu gtt 23

<210> 637

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 637

uuuucuaugc uggugauuaa ctt 23

<210> 638

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 638

uaucaaaguc aguucuacua ctt 23

<210> 639

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 639

cguuaucaaa gucaguucua ctt 23

<210> 640

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 640

agauaacguu aucaaaguca gtt 23

<210> 641

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 641

uuagauaacg uuaucaaagu ctt 23

<210> 642

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 642

gguuagauaa cguuaucaaa gtt 23

<210> 643

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 643

guuaaaaccu cugaaguuaa ctt 23

<210> 644

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 644

acaauccaaa aaugauuagu ctt 23

<210> 645

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 645

uaaguaagac ccuagauuac gtt 23

<210> 646

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 646

guaaguaaga cccuagauua ctt 23

<210> 647

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 647

ugucaucuac gaguaaguaa gtt 23

<210> 648

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 648

gguaauauua guguuuucag gtt 23

<210> 649

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 649

acagguaaua uuaguguuuu ctt 23

<210> 650

<211> 21

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 650

acggcauauu aguuuagugt t 21

<210> 651

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 651

cuuauaauau guaauguuga ctt 23

<210> 652

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 652

gguaacuuau aauauguaau gtt 23

<210> 653

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 653

ccuuaaacca acaaagcuuc ctt 23

<210> 654

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 654

agugccuuaa accaacaaag ctt 23

<210> 655

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 655

ggaaugucaa uaauucuuuc ctt 23

<210> 656

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 656

uaagguuuuu aauauacaac gtt 23

<210> 657

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 657

cuaagguuuu uaauauacaa ctt 23

<210> 658

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 658

guagauuugg uaagacauag gtt 23

<210> 659

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 659

uguagauuug guaagacaua gtt 23

<210> 660

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 660

uuaaguugua gauuugguaa gtt 23

<210> 661

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 661

ccuaaaaguu ggguuaucua ctt 23

<210> 662

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 662

cuauaucuuc guuuaugaca gtt 23

<210> 663

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 663

guaucuauau cuucguuuau gtt 23

<210> 664

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 664

auuccggucc aaguaucuuc ctt 23

<210> 665

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 665

aaagaacuuu agguuagauu ctt 23

<210> 666

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 666

cuuauuucca aagaacuuua gtt 23

<210> 667

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 667

acaguuuugg agcuaacuga ctt 23

<210> 668

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 668

aaaagacaua gacuauagag gtt 23

<210> 669

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 669

aaaaagacau agacuauaga gtt 23

<210> 670

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 670

acaaaaagac auagacuaua gtt 23

<210> 671

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 671

guuaguuaca aaaagacaua gtt 23

<210> 672

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 672

auuauuuccu uucuuaguac ctt 23

<210> 673

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 673

uauuauuucc uuucuuagua ctt 23

<210> 674

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 674

guagucauau uauuuccuuu ctt 23

<210> 675

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 675

agaaaguuac uggaguauga ctt 23

<210> 676

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 676

ucuaaaccuu guaauagaga gtt 23

<210> 677

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 677

agucuaaacc uuguaauaga gtt 23

<210> 678

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 678

ggagucuaaa ccuuguaaua gtt 23

<210> 679

<211> 21

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 679

aacgaugucg guaaacucct t 21

<210> 680

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 680

guuacuuucu caauauaccu ctt 23

<210> 681

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 681

guuguuacuu ucucaauaua ctt 23

<210> 682

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 682

uaacuuuguu guuacuuucu ctt 23

<210> 683

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 683

cguaacuuug uuguuacuuu ctt 23

<210> 684

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 684

guucgauuuc ggagacuaac gtt 23

<210> 685

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 685

gguucgauuu cggagacuaa ctt 23

<210> 686

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 686

acuguuaagg uucgauuucg gtt 23

<210> 687

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 687

agacuguuaa gguucgauuu ctt 23

<210> 688

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 688

agacuuacua gacuguuaag gtt 23

<210> 689

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 689

guuacaagua gucucuucua gtt 23

<210> 690

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 690

ggauaaggua cacaguguua ctt 23

<210> 691

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 691

cuugaagaua gucacaaagu ctt 23

<210> 692

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 692

ucauaacuag gcgucuugaa gtt 23

<210> 693

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 693

agacaagaac ccuagauguu gtt 23

<210> 694

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 694

ccuuucuugc gaguuagaaa ctt 23

<210> 695

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 695

uuauuugcau cgguagugaa gtt 23

<210> 696

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 696

uauagauuuc uuaguaguug gtt 23

<210> 697

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 697

uuaauauaga uuucuuagua gtt 23

<210> 698

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 698

acuaucuuaa aaguuuuugu ctt 23

<210> 699

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 699

auacuaucuu aaaaguuuuu gtt 23

<210> 700

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 700

aaaaaguuua aggauagaug gtt 23

<210> 701

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 701

gaaaaaguuu aaggauagau gtt 23

<210> 702

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 702

acuauaacag agaauaguga ctt 23

<210> 703

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 703

caacuauaac agagaauagu gtt 23

<210> 704

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 704

caacuuuacc guguuaagaa ctt 23

<210> 705

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 705

agacaacuuu accguguuaa gtt 23

<210> 706

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 706

cuuuaaaaga caacuuuacc gtt 23

<210> 707

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 707

ccuuuaaaag acaacuuuac ctt 23

<210> 708

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 708

cuuaaucugu uccguuucua ctt 23

<210> 709

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 709

gguguaaaua acaaaccuuu ctt 23

<210> 710

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 710

gauagugaau gugacaguau ctt 23

<210> 711

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 711

ucaucuaaga uagugaaugu gtt 23

<210> 712

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 712

cuucaucuaa gauagugaau gtt 23

<210> 713

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 713

uuaaaacaca cuucaucuaa gtt 23

<210> 714

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 714

cgauuuaaaa cacacuucau ctt 23

<210> 715

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 715

gaagaucauu aggucaguuu ctt 23

<210> 716

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 716

auuuaagaag aucauuaggu ctt 23

<210> 717

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 717

uuauuuaaga agaucauuag gtt 23

<210> 718

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 718

auuauuuaag aagaucauua gtt 23

<210> 719

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 719

uuuauaugac cgguaucucu ctt 23

<210> 720

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 720

uuaagaaaca cacauguuca gtt 23

<210> 721

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 721

auuuaagaaa cacacauguu ctt 23

<210> 722

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 722

cgagccauuu aagaaacaca ctt 23

<210> 723

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 723

uaacaaugug acaacaaaga ctt 23

<210> 724

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 724

ccuaacaaug ugacaacaaa gtt 23

<210> 725

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 725

aauuugacaa guguuccuaa ctt 23

<210> 726

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 726

gguguagcaa gugguaacag gtt 23

<210> 727

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 727

agacaauaac guguauuuga gtt 23

<210> 728

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 728

gaagacaaua acguguauuu gtt 23

<210> 729

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 729

uuaauacugu aaaacacaua gtt 23

<210> 730

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 730

aaacuuaaua cuguaaaaca ctt 23

<210> 731

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 731

auaaacuuaa uacuguaaaa ctt 23

<210> 732

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 732

uuauguuuau aaacuuaaua ctt 23

<210> 733

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 733

uguuuauuug cgcuccuuau gtt 23

<210> 734

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 734

cguuauucau cccaaaagua gtt 23

<210> 735

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 735

cuaguguuau gguuacaacu ctt 23

<210> 736

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 736

agacaaagaa cuaguguuau gtt 23

<210> 737

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 737

uuuuguuaga caaagaacua gtt 23

<210> 738

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 738

guaaaugugu cucuuugagc ctt 23

<210> 739

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 739

aguaaaugug ucucuuugag ctt 23

<210> 740

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 740

uuaagacuaa gaguagcauc gtt 23

<210> 741

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 741

aguaaaaguc ucguucaaga gtt 23

<210> 742

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 742

cuuauagaaa cccuaugugu ctt 23

<210> 743

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 743

uguccauuug acuaagacaa ctt 23

<210> 744

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 744

guuaucuuug accaauucca ctt 23

<210> 745

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 745

cuuguuaucu uugaccaauu ctt 23

<210> 746

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 746

uaaguaguua uaguuguguu ctt 23

<210> 747

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 747

ugucuacauc cucggauaau gtt 23

<210> 748

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 748

caagcuacaa ugacaaaacg gtt 23

<210> 749

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 749

ccaacgauuu uuacucuauc ctt 23

<210> 750

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 750

uuuaaagagu uuaucauugc ctt 23

<210> 751

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 751

auuuaaagag uuuaucauug ctt 23

<210> 752

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 752

aauuuaaaga guuuaucauu gtt 23

<210> 753

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 753

uaucaauuua aagaguuuau ctt 23

<210> 754

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 754

gguagauauc aauuuaaaga gtt 23

<210> 755

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 755

ucauuuuuau cgguagauau ctt 23

<210> 756

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 756

uuuagauuac gguguuguaa ctt 23

<210> 757

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 757

aguuagguua uguuagagaa gtt 23

<210> 758

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 758

uuuguaagag aguuacugaa ctt 23

<210> 759

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 759

aauacuaaca gaggaacaaa ctt 23

<210> 760

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 760

ucuaauagug ucugaacaac ctt 23

<210> 761

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 761

agaaguuuuu accauuaucg ctt 23

<210> 762

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 762

acagaaguuu uuaccauuau ctt 23

<210> 763

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 763

uauaaacaaa gggaaaaggu gtt 23

<210> 764

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 764

gauaaacuag guaguauaaa ctt 23

<210> 765

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 765

ggauauaccu accaugugua ctt 23

<210> 766

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 766

uguuucuucu gccagaagua gtt 23

<210> 767

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 767

cgacuuaaga cacuucaaca gtt 23

<210> 768

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 768

uguguuacag gugaacaugu gtt 23

<210> 769

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 769

cauguguuac aggugaacau gtt 23

<210> 770

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 770

ccaaaaacgu aagcuuguau ctt 23

<210> 771

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 771

uguaccaaaa acguaagcuu gtt 23

<210> 772

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 772

ccuauguuug uaccaaaaac gtt 23

<210> 773

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 773

gguaguguaa agguuauacc gtt 23

<210> 774

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 774

ccacuucaag aaguagacuu gtt 23

<210> 775

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 775

gauauuuacg ucgcuaacaa ctt 23

<210> 776

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 776

uauaagacau guuccaaauc ctt 23

<210> 777

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 777

guauaagaca uguuccaaau ctt 23

<210> 778

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 778

uauaaguaua agacauguuc ctt 23

<210> 779

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 779

auauaaguau aagacauguu ctt 23

<210> 780

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 780

ugaauauaag uauaagacau gtt 23

<210> 781

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 781

aaauaacguu gggucaagua gtt 23

<210> 782

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 782

uauauaaaag ucguguacaa gtt 23

<210> 783

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 783

uaaauuaacc cauguuaaaa ctt 23

<210> 784

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 784

aguuuuugua accaaagcuu gtt 23

<210> 785

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 785

agacaguuuu uguaaccaaa gtt 23

<210> 786

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 786

aaaagcuuaa gccuguaaca gtt 23

<210> 787

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 787

ucuaauauaa aagcuuaagc ctt 23

<210> 788

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 788

ucucuaauau aaaagcuuaa gtt 23

<210> 789

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 789

ggaguagaac uucuaugaga ctt 23

<210> 790

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 790

cuauauaagg aguagaacuu ctt 23

<210> 791

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 791

gggcucuagg uuuggugcua ucaaatt 27

<210> 792

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 792

gggcucuagg uuuggugcua ucaaatt 27

<210> 793

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 793

gggcucuagg uuuggugcua ucaaatt 27

<210> 794

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 794

gggcucuagg uuuggugcua ucaaa 25

<210> 795

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 795

gggcucuagg uuuggugcua ucaaatt 27

<210> 796

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 796

gggcucuagg uuuggugcua ucaaa 25

<210> 797

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 797

gggcucuagg uuuggugcua ucaaatt 27

<210> 798

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 798

gggcucuagg uuuggugcua ucaaatt 27

<210> 799

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 799

gggcucuagg uuuggugcua ucaaatt 27

<210> 800

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 800

gggcucuagg uuuggugcua ucaaa 25

<210> 801

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 801

gggcucuagg uuuggugcua ucaaa 25

<210> 802

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 802

gggcucuagg uuuggugcua ucaaatt 27

<210> 803

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 803

gggcucuagg uuuggugcua ucaaa 25

<210> 804

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 804

ucuagguuug gugcuaucaa att 23

<210> 805

<211> 17

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 805

uuuggugcua ucaaatt 17

<210> 806

<211> 17

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 806

uuuggugcua ucaaatt 17

<210> 807

<211> 15

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 807

uuuggugcua ucaaa 15

<210> 808

<211> 15

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 808

uuuggugcua ucaaa 15

<210> 809

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 809

uaaguuucaa ccccuacauc ctt 23

<210> 810

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 810

aaagucaaag uccaguugaa gtt 23

<210> 811

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 811

uaaugcauaa agucaaaguc ctt 23

<210> 812

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 812

guaaugcaua aagucaaagu ctt 23

<210> 813

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 813

guucaaaucg guggaguuac gtt 23

<210> 814

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 814

ucuuguauuc gggaucaaac ctt 23

<210> 815

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 815

ugagcuaaaa uccaaggaaa gtt 23

<210> 816

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 816

ggagcuuuug guccuacaac gtt 23

<210> 817

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 817

caaguuuauu agcuaucuuu ctt 23

<210> 818

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 818

guaacaaguu uauuagcuau ctt 23

<210> 819

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 819

aaaauaccaa aguuauugca gtt 23

<210> 820

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 820

auaaaauacc aaaguuauug ctt 23

<210> 821

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 821

uauaaaauac caaaguuauu gtt 23

<210> 822

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 822

ggacugauag gagagucauu gcaaatt 27

<210> 823

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 823

ggacugauag gagagucauu gcaaatt 27

<210> 824

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 824

ggacugauag gagagucauu gcaaatt 27

<210> 825

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 825

ggacugauag gagagucauu gcaaa 25

<210> 826

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 826

ggacugauag gagagucauu gcaaatt 27

<210> 827

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 827

ggacugauag gagagucauu gcaaa 25

<210> 828

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 828

ggacugauag gagagucauu gcaaatt 27

<210> 829

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 829

ggacugauag gagagucauu gcaaatt 27

<210> 830

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 830

ggacugauag gagagucauu gcaaatt 27

<210> 831

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 831

ggacugauag gagagucauu gcaaa 25

<210> 832

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 832

ggacugauag gagagucauu gcaaa 25

<210> 833

<211> 27

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 833

ggacugauag gagagucauu gcaaatt 27

<210> 834

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 834

ggacugauag gagagucauu gcaaa 25

<210> 835

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 835

ugauaggaga gucauugcaa att 23

<210> 836

<211> 17

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 836

gagagucauu gcaaatt 17

<210> 837

<211> 17

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 837

gagagucauu gcaaatt 17

<210> 838

<211> 15

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 838

gagagucauu gcaaa 15

<210> 839

<211> 15

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 839

gagagucauu gcaaa 15

<210> 840

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 840

gaaucuauag gucauauuga ctt 23

<210> 841

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 841

auaaaacaaa gguaugaaga gtt 23

<210> 842

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 842

uuuaaauaaa acaaagguau gtt 23

<210> 843

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 843

gaauaacaua gacucaacua ctt 23

<210> 844

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 844

guaguuuuau cguuaaagga gtt 23

<210> 845

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 845

agaguaguuu uaucguuaaa gtt 23

<210> 846

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 846

gguaaagugu uauaaaaggc ctt 23

<210> 847

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 847

gaaaacuuuu gcgguaaagu gtt 23

<210> 848

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 848

ggaagauauc accuucuuag gtt 23

<210> 849

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 849

guuauaggua caauucuaga ctt 23

<210> 850

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 850

acuguuucag aagugaguaa ctt 23

<210> 851

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 851

agaauaauag guguaaaagu ctt 23

<210> 852

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 852

uaagaauaau agguguaaaa gtt 23

<210> 853

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 853

gaagguauua agaauaauag gtt 23

<210> 854

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 854

ugaagguauu aagaauaaua gtt 23

<210> 855

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 855

cuaaaagcaa acuucucuaa gtt 23

<210> 856

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 856

aaaucuaaaa gcaaacuucu ctt 23

<210> 857

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 857

acaaaucuaa aagcaaacuu ctt 23

<210> 858

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 858

caaacaaauc uaaaagcaaa ctt 23

<210> 859

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 859

ccaucaaaca aaucuaaaag ctt 23

<210> 860

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 860

uaaaaguuuc aaccaucaaa ctt 23

<210> 861

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 861

ucuaaccuaa aaguuucaac ctt 23

<210> 862

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 862

cguaucuaac cuaaaaguuu ctt 23

<210> 863

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 863

gaaauuuuca cagaagacaa ctt 23

<210> 864

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 864

gaagaaauug uucuaaacgc ctt 23

<210> 865

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 865

ucagaagaaa uuguucuaaa ctt 23

<210> 866

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 866

cgaccauauc gauaugaagu ctt 23

<210> 867

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 867

auuaauaagg gauuuaucga ctt 23

<210> 868

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 868

agauuaauaa gggauuuauc gtt 23

<210> 869

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 869

uuuauauaca cguuuucaca ctt 23

<210> 870

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 870

uuuuuauaua cacguuuuca ctt 23

<210> 871

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 871

aauugaaaaa aguagacaaa ctt 23

<210> 872

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 872

guauuucaug acuuacaauu gtt 23

<210> 873

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 873

auaaaaaaag uauuucauga ctt 23

<210> 874

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 874

auauaaaaaa aguauuucau gtt 23

<210> 875

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 875

aauaaacauu uuuauacucu gtt 23

<210> 876

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 876

cauguaacac uauuaauaaa ctt 23

<210> 877

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 877

uauauguaua ucauguaaca ctt 23

<210> 878

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 878

ucuauaugua uaucauguaa ctt 23

<210> 879

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 879

cguuucuaua uguauaucau gtt 23

<210> 880

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 880

cauaauggaa gucuguugaa gtt 23

<210> 881

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 881

auauaaauau cauaauggaa gtt 23

<210> 882

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 882

cuauuagaaa gguuuuaaau gtt 23

<210> 883

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 883

agucauuguc cuauuagaaa gtt 23

<210> 884

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 884

uuuaagucau uguccuauua gtt 23

<210> 885

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 885

uaaucguuua agucauuguc ctt 23

<210> 886

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 886

auaaucguuu aagucauugu ctt 23

<210> 887

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 887

guagaaauaa ucguuuaagu ctt 23

<210> 888

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 888

ccuaguaaau gauauuacua gtt 23

<210> 889

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 889

aaaagaacaa ccuaguaaau gtt 23

<210> 890

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 890

ucaguuaagg aaaagaacaa ctt 23

<210> 891

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 891

auuaaaauau ccuuuauacu ctt 23

<210> 892

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 892

cuauuaaaau auccuuuaua ctt 23

<210> 893

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 893

ucacgauuac acauuuuuac ctt 23

<210> 894

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 894

auaacuugua auuaauucac gtt 23

<210> 895

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 895

uauaacuugu aauuaauuca ctt 23

<210> 896

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 896

auuauaacuu guaauuaauu ctt 23

<210> 897

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 897

aguuuaacug uacauuauaa ctt 23

<210> 898

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 898

gauaguugua ucgguaauua gtt 23

<210> 899

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 899

acagauaugu uguguaucac ctt 23

<210> 900

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 900

ucuacagaua uguuguguau ctt 23

<210> 901

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 901

uuugacuuaa cgaaaaggau gtt 23

<210> 902

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 902

uguuuauuuu uacaacagaa ctt 23

<210> 903

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 903

uguaguguuu auuuuuacaa ctt 23

<210> 904

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 904

aauuacuaua cccuaaagga gtt 23

<210> 905

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 905

auuaauuggu guuugaguua ctt 23

<210> 906

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 906

guaaauuaau ugguguuuga gtt 23

<210> 907

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 907

cuaaaccaaa gucuuuaagu ctt 23

<210> 908

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 908

aaaauacuuc ugugucuaaa ctt 23

<210> 909

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 909

uaaaaguauc uuuguuuuug gtt 23

<210> 910

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 910

auuacuauaa aaguaucuuu gtt 23

<210> 911

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 911

uaauauuacu auaaaaguau ctt 23

<210> 912

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 912

ucacuaauau uacuauaaaa gtt 23

<210> 913

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 913

uuuauuuauc acuaauauua ctt 23

<210> 914

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 914

auuuuucgaa uuauucuuac ctt 23

<210> 915

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 915

uauuuuucga auuauucuua ctt 23

<210> 916

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 916

auauuuacau guguaaaucg gtt 23

<210> 917

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 917

uauauuuaca uguguaaauc gtt 23

<210> 918

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 918

uuauauuuac auguguaaau ctt 23

<210> 919

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 919

guaagauuau auuuacaugu gtt 23

<210> 920

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 920

uauucuuaau uucuuuucua gtt 23

<210> 921

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 921

gguuauucuu aauuucuuuu ctt 23

<210> 922

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 922

uuuuugguua uucuuaauuu ctt 23

<210> 923

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 923

ucugauaugg gugauaaauu ctt 23

<210> 924

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 924

auuguuuaca cguuauaauc gtt 23

<210> 925

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 925

aauuguuuac acguuauaau ctt 23

<210> 926

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 926

uauacaaagu aaguaaguag gtt 23

<210> 927

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 927

agucaucaua uacaaaguaa gtt 23

<210> 928

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 928

uauuagucau cauauacaaa gtt 23

<210> 929

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 929

auuuuauuag ucaucauaua ctt 23

<210> 930

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 930

gauuaguuuc auuaauguca gtt 23

<210> 931

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 931

aauagauuag uuucauuaau gtt 23

<210> 932

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 932

guaauaaagg ucaacaaaua gtt 23

<210> 933

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 933

uaaauaaucu ugaaaaaguc gtt 23

<210> 934

<211> 23

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<220>

<223> description of combined DNA/RNA molecules: synthesis of

Oligonucleotides

<400> 934

guaaauaauc uugaaaaagu ctt 23

<210> 935

<211> 1283

<212> DNA

<213> human

<400> 935

gtgcgcgtgc gcagggataa gagagcggtc tggacagcgc gtggccggcg ccgctgtggg 60

gacagcatga gcggcggttg gatggcgcag gttggagcgt ggcgaacagg ggctctgggc 120

ctggcgctgc tgctgctgct cggcctcgga ctaggcctgg aggccgccgc gagcccgctt 180

tccaccccga cctctgccca ggccgcaggc cccagctcag gctcgtgccc acccaccaag 240

ttccagtgcc gcaccagtgg cttatgcgtg cccctcacct ggcgctgcga cagggacttg 300

gactgcagcg atggcagcga tgaggaggag tgcaggattg agccatgtac ccagaaaggg 360

caatgcccac cgccccctgg cctcccctgc ccctgcaccg gcgtcagtga ctgctctggg 420

ggaactgaca agaaactgcg caactgcagc cgcctggcct gcctagcagg cgagctccgt 480

tgcacgctga gcgatgactg cattccactc acgtggcgct gcgacggcca cccagactgt 540

cccgactcca gcgacgagct cggctgtgga accaatgaga tcctcccgga aggggatgcc 600

acaaccatgg ggccccctgt gaccctggag agtgtcacct ctctcaggaa tgccacaacc 660

atggggcccc ctgtgaccct ggagagtgtc ccctctgtcg ggaatgccac atcctcctct 720

gccggagacc agtctggaag cccaactgcc tatggggtta ttgcagctgc tgcggtgctc 780

agtgcaagcc tggtcaccgc caccctcctc cttttgtcct ggctccgagc ccaggagcgc 840

ctccgcccac tggggttact ggtggccatg aaggagtccc tgctgctgtc agaacagaag 900

acctcgctgc cctgaggaca agcacttgcc accaccgtca ctcagccctg ggcgtagccg 960

gacaggagga gagcagtgat gcggatgggt acccgggcac accagccctc agagacctga 1020

gctcttctgg ccacgtggaa cctcgaaccc gagctcctgc agaagtggcc ctggagattg 1080

agggtccctg gacactccct atggagatcc ggggagctag gatggggaac ctgccacagc 1140

cagaactgag gggctggccc caggcagctc ccagggggta gaacggccct gtgcttaaga 1200

cactcctgct gccccgtctg agggtggcga ttaaagttgc ttcacatcct caaaaaaaaa 1260

aaaaaaaaaa aaaaaaaaaa aaa 1283

<210> 936

<211> 282

<212> PRT

<213> human

<400> 936

Met Ser Gly Gly Trp Met Ala Gln Val Gly Ala Trp Arg Thr Gly Ala

1 5 10 15

Leu Gly Leu Ala Leu Leu Leu Leu Leu Gly Leu Gly Leu Gly Leu Glu

20 25 30

Ala Ala Ala Ser Pro Leu Ser Thr Pro Thr Ser Ala Gln Ala Ala Gly

35 40 45

Pro Ser Ser Gly Ser Cys Pro Pro Thr Lys Phe Gln Cys Arg Thr Ser

50 55 60

Gly Leu Cys Val Pro Leu Thr Trp Arg Cys Asp Arg Asp Leu Asp Cys

65 70 75 80

Ser Asp Gly Ser Asp Glu Glu Glu Cys Arg Ile Glu Pro Cys Thr Gln

85 90 95

Lys Gly Gln Cys Pro Pro Pro Pro Gly Leu Pro Cys Pro Cys Thr Gly

100 105 110

Val Ser Asp Cys Ser Gly Gly Thr Asp Lys Lys Leu Arg Asn Cys Ser

115 120 125

Arg Leu Ala Cys Leu Ala Gly Glu Leu Arg Cys Thr Leu Ser Asp Asp

130 135 140

Cys Ile Pro Leu Thr Trp Arg Cys Asp Gly His Pro Asp Cys Pro Asp

145 150 155 160

Ser Ser Asp Glu Leu Gly Cys Gly Thr Asn Glu Ile Leu Pro Glu Gly

165 170 175

Asp Ala Thr Thr Met Gly Pro Pro Val Thr Leu Glu Ser Val Thr Ser

180 185 190

Leu Arg Asn Ala Thr Thr Met Gly Pro Pro Val Thr Leu Glu Ser Val

195 200 205

Pro Ser Val Gly Asn Ala Thr Ser Ser Ser Ala Gly Asp Gln Ser Gly

210 215 220

Ser Pro Thr Ala Tyr Gly Val Ile Ala Ala Ala Ala Val Leu Ser Ala

225 230 235 240

Ser Leu Val Thr Ala Thr Leu Leu Leu Leu Ser Trp Leu Arg Ala Gln

245 250 255

Glu Arg Leu Arg Pro Leu Gly Leu Leu Val Ala Met Lys Glu Ser Leu

260 265 270

Leu Leu Ser Glu Gln Lys Thr Ser Leu Pro

275 280

<210> 937

<211> 1127

<212> DNA

<213> human

<400> 937

gcgtgcgcgt gcgcagggat aagagagcgg tctggacagc gcgtggccgg cgccgctgtg 60

gggacagcat gagcggcggt tggatggcgc aggttggagc gtggcgaaca ggggctctgg 120

gcctggcgct gctgctgctg ctcggcctcg gactaggcct ggaggccgcc gcgagcccgc 180

tttccacccc gacctctgcc caggccgcag ggattgagcc atgtacccag aaagggcaat 240

gcccaccgcc ccctggcctc ccctgcccct gcaccggcgt cagtgactgc tctgggggaa 300

ctgacaagaa actgcgcaac tgcagccgcc tggcctgcct agcaggcgag ctccgttgca 360

cgctgagcga tgactgcatt ccactcacgt ggcgctgcga cggccaccca gactgtcccg 420

actccagcga cgagctcggc tgtggaacca atgagatcct cccggaaggg gatgccacaa 480

ccatggggcc ccctgtgacc ctggagagtg tcacctctct caggaatgcc acaaccatgg 540

ggccccctgt gaccctggag agtgtcccct ctgtcgggaa tgccacatcc tcctctgccg 600

gagaccagtc tggaagccca actgcctatg gggttattgc agctgctgcg gtgctcagtg 660

caagcctggt caccgccacc ctcctccttt tgtcctggct ccgagcccag gagcgcctcc 720

gcccactggg gttactggtg gccatgaagg agtccctgct gctgtcagaa cagaagacct 780

cgctgccctg aggacaagca cttgccacca ccgtcactca gccctgggcg tagccggaca 840

ggaggagagc agtgatgcgg atgggtaccc gggcacacca gccctcagag acctgagctc 900

ttctggccac gtggaacctc gaacccgagc tcctgcagaa gtggccctgg agattgaggg 960

tccctggaca ctccctatgg agatccgggg agctaggatg gggaacctgc cacagccaga 1020

actgaggggc tggccccagg cagctcccag ggggtagaac ggccctgtgc ttaagacact 1080

cctgctgccc cgtctgaggg tggcaattaa agttgcttca catcctc 1127

<210> 938

<211> 240

<212> PRT

<213> human

<400> 938

Met Ser Gly Gly Trp Met Ala Gln Val Gly Ala Trp Arg Thr Gly Ala

1 5 10 15

Leu Gly Leu Ala Leu Leu Leu Leu Leu Gly Leu Gly Leu Gly Leu Glu

20 25 30

Ala Ala Ala Ser Pro Leu Ser Thr Pro Thr Ser Ala Gln Ala Ala Gly

35 40 45

Ile Glu Pro Cys Thr Gln Lys Gly Gln Cys Pro Pro Pro Pro Gly Leu

50 55 60

Pro Cys Pro Cys Thr Gly Val Ser Asp Cys Ser Gly Gly Thr Asp Lys

65 70 75 80

Lys Leu Arg Asn Cys Ser Arg Leu Ala Cys Leu Ala Gly Glu Leu Arg

85 90 95

Cys Thr Leu Ser Asp Asp Cys Ile Pro Leu Thr Trp Arg Cys Asp Gly

100 105 110

His Pro Asp Cys Pro Asp Ser Ser Asp Glu Leu Gly Cys Gly Thr Asn

115 120 125

Glu Ile Leu Pro Glu Gly Asp Ala Thr Thr Met Gly Pro Pro Val Thr

130 135 140

Leu Glu Ser Val Thr Ser Leu Arg Asn Ala Thr Thr Met Gly Pro Pro

145 150 155 160

Val Thr Leu Glu Ser Val Pro Ser Val Gly Asn Ala Thr Ser Ser Ser

165 170 175

Ala Gly Asp Gln Ser Gly Ser Pro Thr Ala Tyr Gly Val Ile Ala Ala

180 185 190

Ala Ala Val Leu Ser Ala Ser Leu Val Thr Ala Thr Leu Leu Leu Leu

195 200 205

Ser Trp Leu Arg Ala Gln Glu Arg Leu Arg Pro Leu Gly Leu Leu Val

210 215 220

Ala Met Lys Glu Ser Leu Leu Leu Ser Glu Gln Lys Thr Ser Leu Pro

225 230 235 240

<210> 939

<211> 15735

<212> DNA

<213> human

<400> 939

ggtctaaagg gctttatgca ctgtctggag ggtggggact ggcgcgggta gaaaacggga 60

tgcctcgggc gtgggggcag gcttttggcc actaggagct ggcggaggtg cagacctaaa 120

ggagcgttcg ctagcagagg cgctgccggt gcggtgtgct acgcgcgccc acctcccggg 180

gaaggaacgg cgaggccggg gaccgtcgcg gagatggatc gcgggccggc agcagtggcg 240

tgcacgctgc tcctggctct cgtcgcctgc ctagcgccgg ccagtggcca agaatgtgac 300

agtgcgcatt ttcgctgtgg aagtgggcat tgcatccctg cagactggag gtgtgatggg 360

accaaagact gttcagatga cgcggatgaa attggctgcg ctgttgtgac ctgccagcag 420

ggctatttca agtgccagag tgagggacaa tgcatcccca actcctgggt gtgtgaccaa 480

gatcaagact gtgatgatgg ctcagatgaa cgtcaagatt gctcacaaag tacatgctca 540

agtcatcaga taacatgctc caatggtcag tgtatcccaa gtgaatacag gtgcgaccac 600

gtcagagact gccccgatgg agctgatgag aatgactgcc agtacccaac atgtgagcag 660

cttacttgtg acaatggggc ctgctataac accagtcaga agtgtgattg gaaagttgat 720

tgcagggact cctcagatga aatcaactgc actgagatat gcttgcacaa tgagttttca 780

tgtggcaatg gagagtgtat ccctcgtgct tatgtctgtg accatgacaa tgattgccaa 840

gacggcagtg acgaacatgc ttgcaactat ccgacctgcg gtggttacca gttcacttgc 900

cccagtggcc gatgcattta tcaaaactgg gtttgtgatg gagaagatga ctgtaaagat 960

aatggagatg aagatggatg tgaaagcggt cctcatgatg ttcataaatg ttccccaaga 1020

gaatggtctt gcccagagtc gggacgatgc atctccattt ataaagtttg tgatgggatt 1080

ttagattgcc caggaagaga agatgaaaac aacactagta ccggaaaata ctgtagtatg 1140

actctgtgct ctgccttgaa ctgccagtac cagtgccatg agacgccgta tggaggagcg 1200

tgtttttgtc ccccaggtta tatcatcaac cacaatgaca gccgtacctg tgttgagttt 1260

gatgattgcc agatatgggg aatttgtgac cagaagtgtg aaagccgacc tggccgtcac 1320

ctgtgccact gtgaagaagg gtatatcttg gagcgtggac agtattgcaa agctaatgat 1380

tcctttggcg aggcctccat tatcttctcc aatggtcggg atttgttaat tggtgatatt 1440

catggaagga gcttccggat cctagtggag tctcagaatc gtggagtggc cgtgggtgtg 1500

gctttccact atcacctgca aagagttttt tggacagaca ccgtgcaaaa taaggttttt 1560

tcagttgaca ttaatggttt aaatatccaa gaggttctca atgtttctgt tgaaacccca 1620

gagaacctgg ctgtggactg ggttaataat aaaatctatc tagtggaaac caaggtcaac 1680

cgcatagata tggtaaattt ggatggaagc tatcgggtta cccttataac tgaaaacttg 1740

gggcatccta gaggaattgc cgtggaccca actgttggtt atttattttt ctcagattgg 1800

gagagccttt ctggggaacc taagctggaa agggcattca tggatggcag caaccgtaaa 1860

gacttggtga aaacaaagct gggatggcct gctggggtaa ctctggatat gatatcgaag 1920

cgtgtttact gggttgactc tcggtttgat tacattgaaa ctgtaactta tgatggaatt 1980

caaaggaaga ctgtagttca tggaggctcc ctcattcctc atccctttgg agtaagctta 2040

tttgaaggtc aggtgttctt tacagattgg acaaagatgg ccgtgctgaa ggcaaacaag 2100

ttcacagaga ccaacccaca agtgtactac caggcttccc tgaggcccta tggagtgact 2160

gtttaccatt ccctcagaca gccctatgct accaatccgt gtaaagataa caatgggggc 2220

tgtgagcagg tctgtgtcct cagccacaga acagataatg atggtttggg tttccgttgc 2280

aagtgcacat tcggcttcca actggataca gatgagcgcc actgcattgc tgttcagaat 2340

ttcctcattt tttcatccca agttgctatt cgtgggatcc cgttcacctt gtctacccag 2400

gaagatgtca tggttccagt ttcggggaat ccttctttct ttgtcgggat tgattttgac 2460

gcccaggaca gcactatctt tttttcagat atgtcaaaac acatgatttt taagcaaaag 2520

attgatggca caggaagaga aattctcgca gctaacaggg tggaaaatgt tgaaagtttg 2580

gcttttgatt ggatttcaaa gaatctctat tggacagact ctcattacaa gagtatcagt 2640

gtcatgaggc tagctgataa aacgagacgc acagtagttc agtatttaaa taacccacgg 2700

tcggtggtag ttcatccttt tgccgggtat ctattcttca ctgattggtt ccgtcctgct 2760

aaaattatga gagcatggag tgacggatct cacctcttgc ctgtaataaa cactactctt 2820

ggatggccca atggcttggc catcgattgg gctgcttcac gattgtactg ggtagatgcc 2880

tattttgata aaattgagca cagcaccttt gatggtttag acagaagaag actgggccat 2940

atagagcaga tgacacatcc gtttggactt gccatctttg gagagcattt attttttact 3000

gactggagac tgggtgccat tattcgagtc aggaaagcag atggtggaga aatgacagtt 3060

atccgaagtg gcattgctta catactgcat ttgaaatcgt atgatgtcaa catccagact 3120

ggttctaacg cctgtaatca acccacgcat cctaacggtg actgcagcca cttctgcttc 3180

ccggtgccaa atttccagcg agtgtgtggg tgcccttatg gaatgaggct ggcttccaat 3240

cacttgacat gcgaggggga cccaaccaat gaaccaccca cagagcagtg tggcttattt 3300

tccttcccct gtaaaaatgg cagatgtgtg cccaattact atctctgtga tggagtcgat 3360

gattgtcatg ataacagtga tgagcaacta tgtggcacac ttaataatac ctgttcatct 3420

tcggcgttca cctgtggcca tggggagtgc attcctgcac actggcgctg tgacaaacgc 3480

aacgactgtg tggatggcag tgatgagcac aactgcccca cccacgcacc tgcttcctgc 3540

cttgacaccc aatacacctg tgataatcac cagtgtatct caaagaactg ggtctgtgac 3600

acagacaatg attgtgggga tggatctgat gaaaagaact gcaattcgac agagacatgc 3660

caacctagtc agtttaattg ccccaatcat cgatgtattg acctatcgtt tgtctgtgat 3720

ggtgacaagg attgtgttga tggatctgat gaggttggtt gtgtattaaa ctgtactgct 3780

tctcaattca agtgtgccag tggggataaa tgtattggcg tcacaaatcg ttgtgatggt 3840

gtttttgatt gcagtgacaa ctcggatgaa gcaggctgtc caaccaggcc tcctggtatg 3900

tgccactcag atgaatttca gtgccaagaa gatggtatct gcatcccgaa cttctgggaa 3960

tgtgatgggc atccagactg cctctatgga tctgatgagc acaatgcctg tgtccccaag 4020

acttgccctt catcatattt ccactgtgac aacggaaact gcatccacag ggcatggctc 4080

tgtgatcggg acaatgactg cggggatatg agtgatgaga aggactgccc tactcagccc 4140

tttcgctgtc ctagttggca atggcagtgt cttggccata acatctgtgt gaatctgagt 4200

gtagtgtgtg atggcatctt tgactgcccc aatgggacag atgagtcccc actttgcaat 4260

gggaacagct gctcagattt caatggtggt tgtactcacg agtgtgttca agagcccttt 4320

ggggctaaat gcctatgtcc attgggattc ttacttgcca atgattctaa gacctgtgaa 4380

gacatagatg aatgtgatat tctaggctct tgtagccagc actgttacaa tatgagaggt 4440

tctttccggt gctcgtgtga tacaggctac atgttagaaa gtgatgggag gacttgcaaa 4500

gttacagcat ctgagagtct gctgttactt gtggcaagtc agaacaaaat tattgccgac 4560

agtgtcacct cccaggtcca caatatctat tcattggtcg agaatggttc ttacattgta 4620

gctgttgatt ttgattcaat tagtggtcgt atcttttggt ctgatgcaac tcagggtaaa 4680

acctggagtg cgtttcaaaa tggaacggac agaagagtgg tatttgacag tagcatcatc 4740

ttgactgaaa ctattgcaat agattgggta ggtcgtaatc tttactggac agactatgct 4800

ctggaaacaa ttgaagtctc caaaattgat gggagccaca ggactgtgct gattagtaaa 4860

aacctaacaa atccaagagg actagcatta gatcccagaa tgaatgagca tctactgttc 4920

tggtctgact ggggccacca ccctcgcatc gagcgagcca gcatggacgg cagcatgcgc 4980

actgtcattg tccaggacaa gatcttctgg ccctgcggct taactattga ctaccccaac 5040

agactgctct acttcatgga ctcctatctt gattacatgg acttttgtga ttataatgga 5100

caccatcgga gacaggtgat agccagtgat ttgattatac ggcaccccta tgccctaact 5160

ctctttgaag actctgtgta ctggactgac cgtgctactc gtcgggttat gcgagccaac 5220

aagtggcatg gagggaacca gtcagttgta atgtataata ttcaatggcc ccttgggatt 5280

gttgcggttc atccttcgaa acaaccaaat tccgtgaatc catgtgcctt ttcccgctgc 5340

agccatctct gcctgctttc ctcacagggg cctcattttt actcctgtgt ttgtccttca 5400

ggatggagtc tgtctcctga tctcctgaat tgcttgagag atgatcaacc tttcttaata 5460

actgtaaggc aacatataat ttttggaatc tcccttaatc ctgaggtgaa gagcaatgat 5520

gctatggtcc ccatagcagg gatacagaat ggtttagatg ttgaatttga tgatgctgag 5580

caatacatct attgggttga aaatccaggt gaaattcaca gagtgaagac agatggcacc 5640

aacaggacag tatttgcttc tatatctatg gtggggcctt ctatgaacct ggccttagat 5700

tggatttcaa gaaaccttta ttctaccaat cctagaactc agtcaatcga ggttttgaca 5760

ctccacggag atatcagata cagaaaaaca ttgattgcca atgatgggac agctcttgga 5820

gttggctttc caattggcat aactgttgat cctgctcgtg ggaagctgta ctggtcagac 5880

caaggaactg acagtggggt tcctgccaag atcgccagtg ctaacatgga tggcacatct 5940

gtgaaaactc tctttactgg gaacctcgaa cacctggagt gtgtcactct tgacatcgaa 6000

gagcagaaac tctactgggc agtcactgga agaggagtga ttgaaagagg aaacgtggat 6060

ggaacagatc gaatgatcct ggtacaccag ctttcccacc cctggggaat tgcagtccat 6120

gattctttcc tttattatac tgatgaacag tatgaggtca ttgaaagagt tgataaggcc 6180

actggggcca acaaaatagt cttgagagat aatgttccaa atctgagggg tcttcaagtt 6240

tatcacagac gcaatgccgc cgaatcctca aatggctgta gcaacaacat gaatgcctgt 6300

cagcagattt gcctgcctgt accaggagga ttgttttcct gcgcctgtgc cactggattt 6360

aaactcaatc ctgataatcg gtcctgctct ccatataact ctttcattgt tgtttcaatg 6420

ctgtctgcaa tcagaggctt tagcttggaa ttgtcagatc attcagaaac catggtgccg 6480

gtggcaggcc aaggacgaaa cgcactgcat gtggatgtgg atgtgtcctc tggctttatt 6540

tattggtgtg attttagcag ctcagtggca tctgataatg cgatccgtag aattaaacca 6600

gatggatctt ctctgatgaa cattgtgaca catggaatag gagaaaatgg agtccggggt 6660

attgcagtgg attgggtagc aggaaatctt tatttcacca atgcctttgt ttctgaaaca 6720

ctgatagaag ttctgcggat caatactact taccgccgtg ttcttcttaa agtcacagtg 6780

gacatgccta ggcatattgt tgtagatccc aagaacagat acctcttctg ggctgactat 6840

gggcagagac caaagattga gcgttctttc cttgactgta ccaatcgaac agtgcttgtg 6900

tcagagggca ttgtcacacc acggggcttg gcagtggacc gaagtgatgg ctacgtttat 6960

tgggttgatg attctttaga tataattgca aggattcgta tcaatggaga gaactctgaa 7020

gtgattcgtt atggcagtcg ttacccaact ccttatggca tcactgtttt tgaaaattct 7080

atcatatggg tagataggaa tttgaaaaag atcttccaag ccagcaagga accagagaac 7140

acagagccac ccacagtgat aagagacaat atcaactggc taagagatgt gaccatcttt 7200

gacaagcaag tccagccccg gtcaccagca gaggtcaaca acaacccttg cttggaaaac 7260

aatggtgggt gctctcatct ctgctttgct ctgcctggat tgcacacccc aaaatgtgac 7320

tgtgcctttg ggaccctgca aagtgatggc aagaattgtg ccatttcaac agaaaatttc 7380

ctcatctttg ccttgtctaa ttccttgaga agcttacact tggaccctga aaaccatagc 7440

ccacctttcc aaacaataaa tgtggaaaga actgtcatgt ctctagacta tgacagtgta 7500

agtgatagaa tctacttcac acaaaattta gcctctggag ttggacagat ttcctatgcc 7560

accctgtctt cagggatcca tactccaact gtcattgctt caggtatagg gactgctgat 7620

ggcattgcct ttgactggat tactagaaga atttattaca gtgactacct caaccagatg 7680

attaattcca tggctgaaga tgggtctaac cgcactgtga tagcccgcgt tccaaaacca 7740

agagcaattg tgttagatcc ctgccaaggg tacctgtact gggctgactg ggatacacat 7800

gccaaaatcg agagagccac attgggagga aacttccgcg tacccattgt gaacagcagt 7860

ctggtcatgc ccagtgggct gactctggac tatgaagagg accttctcta ctgggtggat 7920

gctagtctgc agaggattga acgcagcact ctgacgggcg tggatcgtga agtcattgtc 7980

aatgcagccg ttcatgcttt tggcttgact ctctatggcc agtatattta ctggactgac 8040

ttgtacacac aaagaattta ccgagctaac aaatatgacg ggtcaggtca gattgcaatg 8100

accacaaatt tgctctccca gcccagggga atcaacactg ttgtgaagaa ccagaaacaa 8160

cagtgtaaca atccttgtga acagtttaat gggggctgca gccatatctg tgcaccaggt 8220

ccaaatggtg ccgagtgcca gtgtccacat gagggcaact ggtatttggc caacaacagg 8280

aagcactgca ttgtggacaa tggtgaacga tgtggtgcat cttccttcac ctgctccaat 8340

gggcgctgca tctcggaaga gtggaagtgt gataatgaca acgactgtgg ggatggcagt 8400

gatgagatgg aaagtgtctg tgcacttcac acctgctcac cgacagcctt cacctgtgcc 8460

aatgggcgat gtgtccaata ctcttaccgc tgtgattact acaatgactg tggtgatggc 8520

agtgatgagg cagggtgcct gttcagggac tgcaatgcca ccacggagtt tatgtgcaat 8580

aacagaaggt gcatacctcg tgagtttatc tgcaatggtg tagacaactg ccatgataat 8640

aacacttcag atgagaaaaa ttgccctgat cgcacttgcc agtctggata cacaaaatgt 8700

cataattcaa atatttgtat tcctcgcgtt tatttgtgtg acggagacaa tgactgtgga 8760

gataacagtg atgaaaaccc tacttattgc accactcaca cgtgcagcag cagtgagttc 8820

caatgcgcat ctgggcgctg tattcctcaa cattggtatt gtgatcaaga aacagattgt 8880

tttgatgcct ctgatgaacc tgcctcttgt ggtcactctg agcgaacatg cctagctgat 8940

gagttcaagt gtgatggtgg gaggtgcatc ccaagcgaat ggatctgtga cggtgataat 9000

gactgtgggg atatgagtga cgaggataaa aggcaccagt gtcagaatca aaactgctcg 9060

gattccgagt ttctctgtgt aaatgacaga cctccggaca ggaggtgcat tccccagtct 9120

tgggtctgtg atggcgatgt ggattgtact gacggctacg atgagaatca gaattgcacc 9180

aggagaactt gctctgaaaa tgaattcacc tgtggttacg gactgtgtat cccaaagata 9240

ttcaggtgtg accggcacaa tgactgtggt gactatagcg acgagagggg ctgcttatac 9300

cagacttgcc aacagaatca gtttacctgt cagaacgggc gctgcattag taaaaccttc 9360

gtctgtgatg aggataatga ctgtggagac ggatctgatg agctgatgca cctgtgccac 9420

accccagaac ccacgtgtcc acctcacgag ttcaagtgtg acaatgggcg ctgcatcgag 9480

atgatgaaac tctgcaacca cctagatgac tgtttggaca acagcgatga gaaaggctgt 9540

ggcattaatg aatgccatga cccttcaatc agtggctgcg atcacaactg cacagacacc 9600

ttaaccagtt tctattgttc ctgtcgtcct ggttacaagc tcatgtctga caagcggact 9660

tgtgttgata ttgatgaatg cacagagatg ccttttgtct gtagccagaa gtgtgagaat 9720

gtaataggct cctacatctg taagtgtgcc ccaggctacc tccgagaacc agatggaaag 9780

acctgccggc aaaacagtaa catcgaaccc tatctcattt ttagcaaccg ttactatttg 9840

agaaatttaa ctatagatgg ctatttttac tccctcatct tggaaggact ggacaatgtt 9900

gtggcattag attttgaccg agtagagaag agattgtatt ggattgatac acagaggcaa 9960

gtcattgaga gaatgtttct gaataagaca aacaaggaga caatcataaa ccacagacta 10020

ccagctgcag aaagtctggc tgtagactgg gtttccagaa agctctactg gttggatgcc 10080

cgcctggatg gcctctttgt ctctgacctc aatggtggac accgccgcat gctggcccag 10140

cactgtgtgg atgccaacaa caccttctgc tttgataatc ccagaggact tgcccttcac 10200

cctcaatatg ggtacctcta ctgggcagac tggggtcacc gcgcatacat tgggagagta 10260

ggcatggatg gaaccaacaa gtctgtgata atctccacca agttagagtg gcctaatggc 10320

atcaccattg attacaccaa tgatctactc tactgggcag atgcccacct gggttacata 10380

gagtactctg atttggaggg ccaccatcga cacacggtgt atgatggggc actgcctcac 10440

cctttcgcta ttaccatttt tgaagacact atttattgga cagattggaa tacaaggaca 10500

gtggaaaagg gaaacaaata tgatggatca aatagacaga cactggtgaa cacaacacac 10560

agaccatttg acatccatgt gtaccatcca tataggcagc ccattgtgag caatccctgt 10620

ggtaccaaca atggtggctg ttctcatctc tgcctcatca agccaggagg aaaagggttc 10680

acttgcgagt gtccagatga cttccgcacc cttcagctga gtggcagcac ctactgcatg 10740

cccatgtgct ccagcaccca gttcctgtgc gctaacaatg aaaagtgcat tcctatctgg 10800

tggaaatgtg atggacagaa agactgctca gatggctctg atgaactggc cctttgcccg 10860

cagcgcttct gccgactggg acagttccag tgcagtgacg gcaactgcac cagcccgcag 10920

actttatgca atgctcacca aaattgccct gatgggtctg atgaagaccg tcttctttgt 10980

gagaatcacc actgtgactc caatgaatgg cagtgcgcca acaaacgttg catcccagaa 11040

tcctggcagt gtgacacatt taacgactgt gaggataact cagatgaaga cagttcccac 11100

tgtgccagca ggacctgccg gccgggccag tttcggtgtg ctaatggccg ctgcatcccg 11160

caggcctgga agtgtgatgt ggataatgat tgtggagacc actcggatga gcccattgaa 11220

gaatgcatga gctctgccca tctctgtgac aacttcacag aattcagctg caaaacaaat 11280

taccgctgca tcccaaagtg ggccgtgtgc aatggtgtag atgactgcag ggacaacagt 11340

gatgagcaag gctgtgagga gaggacatgc catcctgtgg gggatttccg ctgtaaaaat 11400

caccactgca tccctcttcg ttggcagtgt gatgggcaaa atgactgtgg agataactca 11460

gatgaggaaa actgtgctcc ccgggagtgc acagagagcg agtttcgatg tgtcaatcag 11520

cagtgcattc cctcgcgatg gatctgtgac cattacaacg actgtgggga caactcagat 11580

gaacgggact gtgagatgag gacctgccat cctgaatatt ttcagtgtac aagtggacat 11640

tgtgtacaca gtgaactgaa atgcgatgga tccgctgact gtttggatgc gtctgatgaa 11700

gctgattgtc ccacacgctt tcctgatggt gcatactgcc aggctactat gttcgaatgc 11760

aaaaaccatg tttgtatccc gccatattgg aaatgtgatg gcgatgatga ctgtggcgat 11820

ggttcagatg aagaacttca cctgtgcttg gatgttccct gtaattcacc aaaccgtttc 11880

cggtgtgaca acaatcgctg catttatagt catgaggtgt gcaatggtgt ggatgactgt 11940

ggagatggaa ctgatgagac agaggagcac tgtagaaaac cgacccctaa accttgtaca 12000

gaatatgaat ataagtgtgg caatgggcat tgcattccac atgacaatgt gtgtgatgat 12060

gccgatgact gtggtgactg gtccgatgaa ctgggttgca ataaaggaaa agaaagaaca 12120

tgtgctgaaa atatatgcga gcaaaattgt acccaattaa atgaaggagg atttatctgc 12180

tcctgtacag ctgggttcga aaccaatgtt tttgacagaa cctcctgtct agatatcaat 12240

gaatgtgaac aatttgggac ttgtccccag cactgcagaa ataccaaagg aagttatgag 12300

tgtgtctgtg ctgatggctt cacgtctatg agtgaccgcc ctggaaaacg atgtgcagct 12360

gagggtagct ctcctttgtt gctactgcct gacaatgtcc gaattcgaaa atataatctc 12420

tcatctgaga ggttctcaga gtatcttcaa gatgaggaat atatccaagc tgttgattat 12480

gattgggatc ccaaggacat aggcctcagt gttgtgtatt acactgtgcg aggggagggc 12540

tctaggtttg gtgctatcaa acgtgcctac atccccaact ttgaatccgg ccgcaataat 12600

cttgtgcagg aagttgacct gaaactgaaa tacgtaatgc agccagatgg aatagcagtg 12660

gactgggttg gaaggcatat ttactggtca gatgtcaaga ataaacgcat tgaggtggct 12720

aaacttgatg gaaggtacag aaagtggctg atttccactg acctggacca accagctgct 12780

attgctgtga atcccaaact agggcttatg ttctggactg actggggaaa ggaacctaaa 12840

atcgagtctg cctggatgaa tggagaggac cgcaacatcc tggttttcga ggaccttggt 12900

tggccaactg gcctttctat cgattatttg aacaatgacc gaatctactg gagtgacttc 12960

aaggaggacg ttattgaaac cataaaatat gatgggactg ataggagagt cattgcaaag 13020

gaagcaatga acccttacag cctggacatc tttgaagacc agttatactg gatatctaag 13080

gaaaagggag aagtatggaa acaaaataaa tttgggcaag gaaagaaaga gaaaacgctg 13140

gtagtgaacc cttggctcac tcaagttcga atctttcatc aactcagata caataagtca 13200

gtgcccaacc tttgcaaaca gatctgcagc cacctctgcc ttctgagacc tggaggatac 13260

agctgtgcct gtccccaagg ctccagcttt atagagggga gcaccactga gtgtgatgca 13320

gccatcgaac tgcctatcaa cctgcccccc ccatgcaggt gcatgcacgg aggaaattgc 13380

tattttgatg agactgacct ccccaaatgc aagtgtccta gcggctacac cggaaaatat 13440

tgtgaaatgg cgttttcaaa aggcatctct ccaggaacaa ccgcagtagc tgtgctgttg 13500

acaatcctct tgatcgtcgt aattggagct ctggcaattg caggattctt ccactataga 13560

aggaccggct cccttttgcc tgctctgccc aagctgccaa gcttaagcag tctcgtcaag 13620

ccctctgaaa atgggaatgg ggtgaccttc agatcagggg cagatcttaa catggatatt 13680

ggagtgtctg gttttggacc tgagactgct attgacaggt caatggcaat gagtgaagac 13740

tttgtcatgg aaatggggaa gcagcccata atatttgaaa acccaatgta ctcagccaga 13800

gacagtgctg tcaaagtggt tcagccaatc caggtgactg tatctgaaaa tgtggataat 13860

aagaattatg gaagtcccat aaacccttct gagatagttc cagagacaaa cccaacttca 13920

ccagctgctg atggaactca ggtgacaaaa tggaatctct tcaaacgaaa atctaaacaa 13980

actaccaact ttgaaaatcc aatctatgca cagatggaga acgagcaaaa ggaaagtgtt 14040

gctgcgacac cacctccatc accttcgctc cctgctaagc ctaagcctcc ttcgagaaga 14100

gacccaactc caacctattc tgcaacagaa gacactttta aagacaccgc aaatcttgtt 14160

aaagaagact ctgaagtata gctataccag ctatttaggg aataattaga aacacacttt 14220

tgcacatata ttttttacaa acagatgaaa aaagttaaca ttcagtactt tatgaaaaaa 14280

atatattttt ccctgtttgc ctatagttgg aggtatcctg tgtgtctttt tttacttatg 14340

ccgtctcata tttttacaaa taattatcac aatgtactat atgtatatct ttgcactgaa 14400

gttgtctgaa ggtaatacta taaatatatt gtatatttgt aaattttgga aagattatcc 14460

tgttactgaa tttgctaata aagatgtctg ctgatttggt tggtgatcat tatagtaaat 14520

gatccaacaa gaaaaggaat tgactgggga cctttagccg tgtctaaaga agaggcacca 14580

ctcatatttc ctataaaatt atctaggaaa ggaatccagg ccccgctctt gggtccattt 14640

ttacacatta gcacttaatt aatgttcaat attacatgtc aatttgatta atggctatgt 14700

tgataggggc cactatgtgt tgtatagaca tctggacttg actgtagact cctcagataa 14760

tacagaaggt aggaaaagca attcagtttg gcccttctgt gtgttggcat tgtctaacca 14820

gaactctctg tttcatgtgt gttctctcac tagctgccaa gacaacattt ttatttgtga 14880

tgtctatgag gaaatcccat atcattaagt gccagtgtcc tgcattgagt ttgtggttaa 14940

ttaaatgagc tcttctgctg atggaccctg gagcaatttc tcccctcacc tgacattcaa 15000

ggtggtcacc tgccctagta gttggagctc agtagctgaa tttctgaaac caaatctgtg 15060

tcttcataaa ataaggtgca aaaaaaaaaa ataccagtta agtaaagcct caactgggtt 15120

tttgtttcta tgaaaatatc attataatca ctatttattt cctaagttga acctgaatag 15180

aaagggaaac cattcttatt aagcttttta ttaggccctg tggctaaatg tgtacattta 15240

tattagaatg tactgtacag tccagatctt ttctttaatt cttattggtt tttttttttt 15300

tttttttttt agagatggag tcttgctata ttgccaaggc tgatcttgaa gtcctgggct 15360

caagtgatcc tcccacctca gcctcctgag tggttggggt tacgggcgtg agccactgtg 15420

cctggcttcc agctctcctc ttaaatagtg ggtatagtct gcacaacagg aaccatggca 15480

ggaatataca ctttcccata gcaaatagca tacctgactc tctgtgctaa tattgcacat 15540

ttgttaaaca atgaatgaat ggatggatgg atggatggat gaatgaatga aacatatact 15600

actgattatt ttattccaga gttctcaaaa tatttgttgc tgatattttg agtgctgact 15660

gtaattactt tgattagata aacaactgga aataatgctg ctgaaaaagt tctaataaat 15720

gtgtatttta tcaga 15735

<210> 940

<211> 4655

<212> PRT

<213> human

<400> 940

Met Asp Arg Gly Pro Ala Ala Val Ala Cys Thr Leu Leu Leu Ala Leu

1 5 10 15

Val Ala Cys Leu Ala Pro Ala Ser Gly Gln Glu Cys Asp Ser Ala His

20 25 30

Phe Arg Cys Gly Ser Gly His Cys Ile Pro Ala Asp Trp Arg Cys Asp

35 40 45

Gly Thr Lys Asp Cys Ser Asp Asp Ala Asp Glu Ile Gly Cys Ala Val

50 55 60

Val Thr Cys Gln Gln Gly Tyr Phe Lys Cys Gln Ser Glu Gly Gln Cys

65 70 75 80

Ile Pro Asn Ser Trp Val Cys Asp Gln Asp Gln Asp Cys Asp Asp Gly

85 90 95

Ser Asp Glu Arg Gln Asp Cys Ser Gln Ser Thr Cys Ser Ser His Gln

100 105 110

Ile Thr Cys Ser Asn Gly Gln Cys Ile Pro Ser Glu Tyr Arg Cys Asp

115 120 125

His Val Arg Asp Cys Pro Asp Gly Ala Asp Glu Asn Asp Cys Gln Tyr

130 135 140

Pro Thr Cys Glu Gln Leu Thr Cys Asp Asn Gly Ala Cys Tyr Asn Thr

145 150 155 160

Ser Gln Lys Cys Asp Trp Lys Val Asp Cys Arg Asp Ser Ser Asp Glu

165 170 175

Ile Asn Cys Thr Glu Ile Cys Leu His Asn Glu Phe Ser Cys Gly Asn

180 185 190

Gly Glu Cys Ile Pro Arg Ala Tyr Val Cys Asp His Asp Asn Asp Cys

195 200 205

Gln Asp Gly Ser Asp Glu His Ala Cys Asn Tyr Pro Thr Cys Gly Gly

210 215 220

Tyr Gln Phe Thr Cys Pro Ser Gly Arg Cys Ile Tyr Gln Asn Trp Val

225 230 235 240

Cys Asp Gly Glu Asp Asp Cys Lys Asp Asn Gly Asp Glu Asp Gly Cys

245 250 255

Glu Ser Gly Pro His Asp Val His Lys Cys Ser Pro Arg Glu Trp Ser

260 265 270

Cys Pro Glu Ser Gly Arg Cys Ile Ser Ile Tyr Lys Val Cys Asp Gly

275 280 285

Ile Leu Asp Cys Pro Gly Arg Glu Asp Glu Asn Asn Thr Ser Thr Gly

290 295 300

Lys Tyr Cys Ser Met Thr Leu Cys Ser Ala Leu Asn Cys Gln Tyr Gln

305 310 315 320

Cys His Glu Thr Pro Tyr Gly Gly Ala Cys Phe Cys Pro Pro Gly Tyr

325 330 335

Ile Ile Asn His Asn Asp Ser Arg Thr Cys Val Glu Phe Asp Asp Cys

340 345 350

Gln Ile Trp Gly Ile Cys Asp Gln Lys Cys Glu Ser Arg Pro Gly Arg

355 360 365

His Leu Cys His Cys Glu Glu Gly Tyr Ile Leu Glu Arg Gly Gln Tyr

370 375 380

Cys Lys Ala Asn Asp Ser Phe Gly Glu Ala Ser Ile Ile Phe Ser Asn

385 390 395 400

Gly Arg Asp Leu Leu Ile Gly Asp Ile His Gly Arg Ser Phe Arg Ile

405 410 415

Leu Val Glu Ser Gln Asn Arg Gly Val Ala Val Gly Val Ala Phe His

420 425 430

Tyr His Leu Gln Arg Val Phe Trp Thr Asp Thr Val Gln Asn Lys Val

435 440 445

Phe Ser Val Asp Ile Asn Gly Leu Asn Ile Gln Glu Val Leu Asn Val

450 455 460

Ser Val Glu Thr Pro Glu Asn Leu Ala Val Asp Trp Val Asn Asn Lys

465 470 475 480

Ile Tyr Leu Val Glu Thr Lys Val Asn Arg Ile Asp Met Val Asn Leu

485 490 495

Asp Gly Ser Tyr Arg Val Thr Leu Ile Thr Glu Asn Leu Gly His Pro

500 505 510

Arg Gly Ile Ala Val Asp Pro Thr Val Gly Tyr Leu Phe Phe Ser Asp

515 520 525

Trp Glu Ser Leu Ser Gly Glu Pro Lys Leu Glu Arg Ala Phe Met Asp

530 535 540

Gly Ser Asn Arg Lys Asp Leu Val Lys Thr Lys Leu Gly Trp Pro Ala

545 550 555 560

Gly Val Thr Leu Asp Met Ile Ser Lys Arg Val Tyr Trp Val Asp Ser

565 570 575

Arg Phe Asp Tyr Ile Glu Thr Val Thr Tyr Asp Gly Ile Gln Arg Lys

580 585 590

Thr Val Val His Gly Gly Ser Leu Ile Pro His Pro Phe Gly Val Ser

595 600 605

Leu Phe Glu Gly Gln Val Phe Phe Thr Asp Trp Thr Lys Met Ala Val

610 615 620

Leu Lys Ala Asn Lys Phe Thr Glu Thr Asn Pro Gln Val Tyr Tyr Gln

625 630 635 640

Ala Ser Leu Arg Pro Tyr Gly Val Thr Val Tyr His Ser Leu Arg Gln

645 650 655

Pro Tyr Ala Thr Asn Pro Cys Lys Asp Asn Asn Gly Gly Cys Glu Gln

660 665 670

Val Cys Val Leu Ser His Arg Thr Asp Asn Asp Gly Leu Gly Phe Arg

675 680 685

Cys Lys Cys Thr Phe Gly Phe Gln Leu Asp Thr Asp Glu Arg His Cys

690 695 700

Ile Ala Val Gln Asn Phe Leu Ile Phe Ser Ser Gln Val Ala Ile Arg

705 710 715 720

Gly Ile Pro Phe Thr Leu Ser Thr Gln Glu Asp Val Met Val Pro Val

725 730 735

Ser Gly Asn Pro Ser Phe Phe Val Gly Ile Asp Phe Asp Ala Gln Asp

740 745 750

Ser Thr Ile Phe Phe Ser Asp Met Ser Lys His Met Ile Phe Lys Gln

755 760 765

Lys Ile Asp Gly Thr Gly Arg Glu Ile Leu Ala Ala Asn Arg Val Glu

770 775 780

Asn Val Glu Ser Leu Ala Phe Asp Trp Ile Ser Lys Asn Leu Tyr Trp

785 790 795 800

Thr Asp Ser His Tyr Lys Ser Ile Ser Val Met Arg Leu Ala Asp Lys

805 810 815

Thr Arg Arg Thr Val Val Gln Tyr Leu Asn Asn Pro Arg Ser Val Val

820 825 830

Val His Pro Phe Ala Gly Tyr Leu Phe Phe Thr Asp Trp Phe Arg Pro

835 840 845

Ala Lys Ile Met Arg Ala Trp Ser Asp Gly Ser His Leu Leu Pro Val

850 855 860

Ile Asn Thr Thr Leu Gly Trp Pro Asn Gly Leu Ala Ile Asp Trp Ala

865 870 875 880

Ala Ser Arg Leu Tyr Trp Val Asp Ala Tyr Phe Asp Lys Ile Glu His

885 890 895

Ser Thr Phe Asp Gly Leu Asp Arg Arg Arg Leu Gly His Ile Glu Gln

900 905 910

Met Thr His Pro Phe Gly Leu Ala Ile Phe Gly Glu His Leu Phe Phe

915 920 925

Thr Asp Trp Arg Leu Gly Ala Ile Ile Arg Val Arg Lys Ala Asp Gly

930 935 940

Gly Glu Met Thr Val Ile Arg Ser Gly Ile Ala Tyr Ile Leu His Leu

945 950 955 960

Lys Ser Tyr Asp Val Asn Ile Gln Thr Gly Ser Asn Ala Cys Asn Gln

965 970 975

Pro Thr His Pro Asn Gly Asp Cys Ser His Phe Cys Phe Pro Val Pro

980 985 990

Asn Phe Gln Arg Val Cys Gly Cys Pro Tyr Gly Met Arg Leu Ala Ser

995 1000 1005

Asn His Leu Thr Cys Glu Gly Asp Pro Thr Asn Glu Pro Pro Thr

1010 1015 1020

Glu Gln Cys Gly Leu Phe Ser Phe Pro Cys Lys Asn Gly Arg Cys

1025 1030 1035

Val Pro Asn Tyr Tyr Leu Cys Asp Gly Val Asp Asp Cys His Asp

1040 1045 1050

Asn Ser Asp Glu Gln Leu Cys Gly Thr Leu Asn Asn Thr Cys Ser

1055 1060 1065

Ser Ser Ala Phe Thr Cys Gly His Gly Glu Cys Ile Pro Ala His

1070 1075 1080

Trp Arg Cys Asp Lys Arg Asn Asp Cys Val Asp Gly Ser Asp Glu

1085 1090 1095

His Asn Cys Pro Thr His Ala Pro Ala Ser Cys Leu Asp Thr Gln

1100 1105 1110

Tyr Thr Cys Asp Asn His Gln Cys Ile Ser Lys Asn Trp Val Cys

1115 1120 1125

Asp Thr Asp Asn Asp Cys Gly Asp Gly Ser Asp Glu Lys Asn Cys

1130 1135 1140

Asn Ser Thr Glu Thr Cys Gln Pro Ser Gln Phe Asn Cys Pro Asn

1145 1150 1155

His Arg Cys Ile Asp Leu Ser Phe Val Cys Asp Gly Asp Lys Asp

1160 1165 1170

Cys Val Asp Gly Ser Asp Glu Val Gly Cys Val Leu Asn Cys Thr

1175 1180 1185

Ala Ser Gln Phe Lys Cys Ala Ser Gly Asp Lys Cys Ile Gly Val

1190 1195 1200

Thr Asn Arg Cys Asp Gly Val Phe Asp Cys Ser Asp Asn Ser Asp

1205 1210 1215

Glu Ala Gly Cys Pro Thr Arg Pro Pro Gly Met Cys His Ser Asp

1220 1225 1230

Glu Phe Gln Cys Gln Glu Asp Gly Ile Cys Ile Pro Asn Phe Trp

1235 1240 1245

Glu Cys Asp Gly His Pro Asp Cys Leu Tyr Gly Ser Asp Glu His

1250 1255 1260

Asn Ala Cys Val Pro Lys Thr Cys Pro Ser Ser Tyr Phe His Cys

1265 1270 1275

Asp Asn Gly Asn Cys Ile His Arg Ala Trp Leu Cys Asp Arg Asp

1280 1285 1290

Asn Asp Cys Gly Asp Met Ser Asp Glu Lys Asp Cys Pro Thr Gln

1295 1300 1305

Pro Phe Arg Cys Pro Ser Trp Gln Trp Gln Cys Leu Gly His Asn

1310 1315 1320

Ile Cys Val Asn Leu Ser Val Val Cys Asp Gly Ile Phe Asp Cys

1325 1330 1335

Pro Asn Gly Thr Asp Glu Ser Pro Leu Cys Asn Gly Asn Ser Cys

1340 1345 1350

Ser Asp Phe Asn Gly Gly Cys Thr His Glu Cys Val Gln Glu Pro

1355 1360 1365

Phe Gly Ala Lys Cys Leu Cys Pro Leu Gly Phe Leu Leu Ala Asn

1370 1375 1380

Asp Ser Lys Thr Cys Glu Asp Ile Asp Glu Cys Asp Ile Leu Gly

1385 1390 1395

Ser Cys Ser Gln His Cys Tyr Asn Met Arg Gly Ser Phe Arg Cys

1400 1405 1410

Ser Cys Asp Thr Gly Tyr Met Leu Glu Ser Asp Gly Arg Thr Cys

1415 1420 1425

Lys Val Thr Ala Ser Glu Ser Leu Leu Leu Leu Val Ala Ser Gln

1430 1435 1440

Asn Lys Ile Ile Ala Asp Ser Val Thr Ser Gln Val His Asn Ile

1445 1450 1455

Tyr Ser Leu Val Glu Asn Gly Ser Tyr Ile Val Ala Val Asp Phe

1460 1465 1470

Asp Ser Ile Ser Gly Arg Ile Phe Trp Ser Asp Ala Thr Gln Gly

1475 1480 1485

Lys Thr Trp Ser Ala Phe Gln Asn Gly Thr Asp Arg Arg Val Val

1490 1495 1500

Phe Asp Ser Ser Ile Ile Leu Thr Glu Thr Ile Ala Ile Asp Trp

1505 1510 1515

Val Gly Arg Asn Leu Tyr Trp Thr Asp Tyr Ala Leu Glu Thr Ile

1520 1525 1530

Glu Val Ser Lys Ile Asp Gly Ser His Arg Thr Val Leu Ile Ser

1535 1540 1545

Lys Asn Leu Thr Asn Pro Arg Gly Leu Ala Leu Asp Pro Arg Met

1550 1555 1560

Asn Glu His Leu Leu Phe Trp Ser Asp Trp Gly His His Pro Arg

1565 1570 1575

Ile Glu Arg Ala Ser Met Asp Gly Ser Met Arg Thr Val Ile Val

1580 1585 1590

Gln Asp Lys Ile Phe Trp Pro Cys Gly Leu Thr Ile Asp Tyr Pro

1595 1600 1605

Asn Arg Leu Leu Tyr Phe Met Asp Ser Tyr Leu Asp Tyr Met Asp

1610 1615 1620

Phe Cys Asp Tyr Asn Gly His His Arg Arg Gln Val Ile Ala Ser

1625 1630 1635

Asp Leu Ile Ile Arg His Pro Tyr Ala Leu Thr Leu Phe Glu Asp

1640 1645 1650

Ser Val Tyr Trp Thr Asp Arg Ala Thr Arg Arg Val Met Arg Ala

1655 1660 1665

Asn Lys Trp His Gly Gly Asn Gln Ser Val Val Met Tyr Asn Ile

1670 1675 1680

Gln Trp Pro Leu Gly Ile Val Ala Val His Pro Ser Lys Gln Pro

1685 1690 1695

Asn Ser Val Asn Pro Cys Ala Phe Ser Arg Cys Ser His Leu Cys

1700 1705 1710

Leu Leu Ser Ser Gln Gly Pro His Phe Tyr Ser Cys Val Cys Pro

1715 1720 1725

Ser Gly Trp Ser Leu Ser Pro Asp Leu Leu Asn Cys Leu Arg Asp

1730 1735 1740

Asp Gln Pro Phe Leu Ile Thr Val Arg Gln His Ile Ile Phe Gly

1745 1750 1755

Ile Ser Leu Asn Pro Glu Val Lys Ser Asn Asp Ala Met Val Pro

1760 1765 1770

Ile Ala Gly Ile Gln Asn Gly Leu Asp Val Glu Phe Asp Asp Ala

1775 1780 1785

Glu Gln Tyr Ile Tyr Trp Val Glu Asn Pro Gly Glu Ile His Arg

1790 1795 1800

Val Lys Thr Asp Gly Thr Asn Arg Thr Val Phe Ala Ser Ile Ser

1805 1810 1815

Met Val Gly Pro Ser Met Asn Leu Ala Leu Asp Trp Ile Ser Arg

1820 1825 1830

Asn Leu Tyr Ser Thr Asn Pro Arg Thr Gln Ser Ile Glu Val Leu

1835 1840 1845

Thr Leu His Gly Asp Ile Arg Tyr Arg Lys Thr Leu Ile Ala Asn

1850 1855 1860

Asp Gly Thr Ala Leu Gly Val Gly Phe Pro Ile Gly Ile Thr Val

1865 1870 1875

Asp Pro Ala Arg Gly Lys Leu Tyr Trp Ser Asp Gln Gly Thr Asp

1880 1885 1890

Ser Gly Val Pro Ala Lys Ile Ala Ser Ala Asn Met Asp Gly Thr

1895 1900 1905

Ser Val Lys Thr Leu Phe Thr Gly Asn Leu Glu His Leu Glu Cys

1910 1915 1920

Val Thr Leu Asp Ile Glu Glu Gln Lys Leu Tyr Trp Ala Val Thr

1925 1930 1935

Gly Arg Gly Val Ile Glu Arg Gly Asn Val Asp Gly Thr Asp Arg

1940 1945 1950

Met Ile Leu Val His Gln Leu Ser His Pro Trp Gly Ile Ala Val

1955 1960 1965

His Asp Ser Phe Leu Tyr Tyr Thr Asp Glu Gln Tyr Glu Val Ile

1970 1975 1980

Glu Arg Val Asp Lys Ala Thr Gly Ala Asn Lys Ile Val Leu Arg

1985 1990 1995

Asp Asn Val Pro Asn Leu Arg Gly Leu Gln Val Tyr His Arg Arg

2000 2005 2010

Asn Ala Ala Glu Ser Ser Asn Gly Cys Ser Asn Asn Met Asn Ala

2015 2020 2025

Cys Gln Gln Ile Cys Leu Pro Val Pro Gly Gly Leu Phe Ser Cys

2030 2035 2040

Ala Cys Ala Thr Gly Phe Lys Leu Asn Pro Asp Asn Arg Ser Cys

2045 2050 2055

Ser Pro Tyr Asn Ser Phe Ile Val Val Ser Met Leu Ser Ala Ile

2060 2065 2070

Arg Gly Phe Ser Leu Glu Leu Ser Asp His Ser Glu Thr Met Val

2075 2080 2085

Pro Val Ala Gly Gln Gly Arg Asn Ala Leu His Val Asp Val Asp

2090 2095 2100

Val Ser Ser Gly Phe Ile Tyr Trp Cys Asp Phe Ser Ser Ser Val

2105 2110 2115

Ala Ser Asp Asn Ala Ile Arg Arg Ile Lys Pro Asp Gly Ser Ser

2120 2125 2130

Leu Met Asn Ile Val Thr His Gly Ile Gly Glu Asn Gly Val Arg

2135 2140 2145

Gly Ile Ala Val Asp Trp Val Ala Gly Asn Leu Tyr Phe Thr Asn

2150 2155 2160

Ala Phe Val Ser Glu Thr Leu Ile Glu Val Leu Arg Ile Asn Thr

2165 2170 2175

Thr Tyr Arg Arg Val Leu Leu Lys Val Thr Val Asp Met Pro Arg

2180 2185 2190

His Ile Val Val Asp Pro Lys Asn Arg Tyr Leu Phe Trp Ala Asp

2195 2200 2205

Tyr Gly Gln Arg Pro Lys Ile Glu Arg Ser Phe Leu Asp Cys Thr

2210 2215 2220

Asn Arg Thr Val Leu Val Ser Glu Gly Ile Val Thr Pro Arg Gly

2225 2230 2235

Leu Ala Val Asp Arg Ser Asp Gly Tyr Val Tyr Trp Val Asp Asp

2240 2245 2250

Ser Leu Asp Ile Ile Ala Arg Ile Arg Ile Asn Gly Glu Asn Ser

2255 2260 2265

Glu Val Ile Arg Tyr Gly Ser Arg Tyr Pro Thr Pro Tyr Gly Ile

2270 2275 2280

Thr Val Phe Glu Asn Ser Ile Ile Trp Val Asp Arg Asn Leu Lys

2285 2290 2295

Lys Ile Phe Gln Ala Ser Lys Glu Pro Glu Asn Thr Glu Pro Pro

2300 2305 2310

Thr Val Ile Arg Asp Asn Ile Asn Trp Leu Arg Asp Val Thr Ile

2315 2320 2325

Phe Asp Lys Gln Val Gln Pro Arg Ser Pro Ala Glu Val Asn Asn

2330 2335 2340

Asn Pro Cys Leu Glu Asn Asn Gly Gly Cys Ser His Leu Cys Phe

2345 2350 2355

Ala Leu Pro Gly Leu His Thr Pro Lys Cys Asp Cys Ala Phe Gly

2360 2365 2370

Thr Leu Gln Ser Asp Gly Lys Asn Cys Ala Ile Ser Thr Glu Asn

2375 2380 2385

Phe Leu Ile Phe Ala Leu Ser Asn Ser Leu Arg Ser Leu His Leu

2390 2395 2400

Asp Pro Glu Asn His Ser Pro Pro Phe Gln Thr Ile Asn Val Glu

2405 2410 2415

Arg Thr Val Met Ser Leu Asp Tyr Asp Ser Val Ser Asp Arg Ile

2420 2425 2430

Tyr Phe Thr Gln Asn Leu Ala Ser Gly Val Gly Gln Ile Ser Tyr

2435 2440 2445

Ala Thr Leu Ser Ser Gly Ile His Thr Pro Thr Val Ile Ala Ser

2450 2455 2460

Gly Ile Gly Thr Ala Asp Gly Ile Ala Phe Asp Trp Ile Thr Arg

2465 2470 2475

Arg Ile Tyr Tyr Ser Asp Tyr Leu Asn Gln Met Ile Asn Ser Met

2480 2485 2490

Ala Glu Asp Gly Ser Asn Arg Thr Val Ile Ala Arg Val Pro Lys

2495 2500 2505

Pro Arg Ala Ile Val Leu Asp Pro Cys Gln Gly Tyr Leu Tyr Trp

2510 2515 2520

Ala Asp Trp Asp Thr His Ala Lys Ile Glu Arg Ala Thr Leu Gly

2525 2530 2535

Gly Asn Phe Arg Val Pro Ile Val Asn Ser Ser Leu Val Met Pro

2540 2545 2550

Ser Gly Leu Thr Leu Asp Tyr Glu Glu Asp Leu Leu Tyr Trp Val

2555 2560 2565

Asp Ala Ser Leu Gln Arg Ile Glu Arg Ser Thr Leu Thr Gly Val

2570 2575 2580

Asp Arg Glu Val Ile Val Asn Ala Ala Val His Ala Phe Gly Leu

2585 2590 2595

Thr Leu Tyr Gly Gln Tyr Ile Tyr Trp Thr Asp Leu Tyr Thr Gln

2600 2605 2610

Arg Ile Tyr Arg Ala Asn Lys Tyr Asp Gly Ser Gly Gln Ile Ala

2615 2620 2625

Met Thr Thr Asn Leu Leu Ser Gln Pro Arg Gly Ile Asn Thr Val

2630 2635 2640

Val Lys Asn Gln Lys Gln Gln Cys Asn Asn Pro Cys Glu Gln Phe

2645 2650 2655

Asn Gly Gly Cys Ser His Ile Cys Ala Pro Gly Pro Asn Gly Ala

2660 2665 2670

Glu Cys Gln Cys Pro His Glu Gly Asn Trp Tyr Leu Ala Asn Asn

2675 2680 2685

Arg Lys His Cys Ile Val Asp Asn Gly Glu Arg Cys Gly Ala Ser

2690 2695 2700

Ser Phe Thr Cys Ser Asn Gly Arg Cys Ile Ser Glu Glu Trp Lys

2705 2710 2715

Cys Asp Asn Asp Asn Asp Cys Gly Asp Gly Ser Asp Glu Met Glu

2720 2725 2730

Ser Val Cys Ala Leu His Thr Cys Ser Pro Thr Ala Phe Thr Cys

2735 2740 2745

Ala Asn Gly Arg Cys Val Gln Tyr Ser Tyr Arg Cys Asp Tyr Tyr

2750 2755 2760

Asn Asp Cys Gly Asp Gly Ser Asp Glu Ala Gly Cys Leu Phe Arg

2765 2770 2775

Asp Cys Asn Ala Thr Thr Glu Phe Met Cys Asn Asn Arg Arg Cys

2780 2785 2790

Ile Pro Arg Glu Phe Ile Cys Asn Gly Val Asp Asn Cys His Asp

2795 2800 2805

Asn Asn Thr Ser Asp Glu Lys Asn Cys Pro Asp Arg Thr Cys Gln

2810 2815 2820

Ser Gly Tyr Thr Lys Cys His Asn Ser Asn Ile Cys Ile Pro Arg

2825 2830 2835

Val Tyr Leu Cys Asp Gly Asp Asn Asp Cys Gly Asp Asn Ser Asp

2840 2845 2850

Glu Asn Pro Thr Tyr Cys Thr Thr His Thr Cys Ser Ser Ser Glu

2855 2860 2865

Phe Gln Cys Ala Ser Gly Arg Cys Ile Pro Gln His Trp Tyr Cys

2870 2875 2880

Asp Gln Glu Thr Asp Cys Phe Asp Ala Ser Asp Glu Pro Ala Ser

2885 2890 2895

Cys Gly His Ser Glu Arg Thr Cys Leu Ala Asp Glu Phe Lys Cys

2900 2905 2910

Asp Gly Gly Arg Cys Ile Pro Ser Glu Trp Ile Cys Asp Gly Asp

2915 2920 2925

Asn Asp Cys Gly Asp Met Ser Asp Glu Asp Lys Arg His Gln Cys

2930 2935 2940

Gln Asn Gln Asn Cys Ser Asp Ser Glu Phe Leu Cys Val Asn Asp

2945 2950 2955

Arg Pro Pro Asp Arg Arg Cys Ile Pro Gln Ser Trp Val Cys Asp

2960 2965 2970

Gly Asp Val Asp Cys Thr Asp Gly Tyr Asp Glu Asn Gln Asn Cys

2975 2980 2985

Thr Arg Arg Thr Cys Ser Glu Asn Glu Phe Thr Cys Gly Tyr Gly

2990 2995 3000

Leu Cys Ile Pro Lys Ile Phe Arg Cys Asp Arg His Asn Asp Cys

3005 3010 3015

Gly Asp Tyr Ser Asp Glu Arg Gly Cys Leu Tyr Gln Thr Cys Gln

3020 3025 3030

Gln Asn Gln Phe Thr Cys Gln Asn Gly Arg Cys Ile Ser Lys Thr

3035 3040 3045

Phe Val Cys Asp Glu Asp Asn Asp Cys Gly Asp Gly Ser Asp Glu

3050 3055 3060

Leu Met His Leu Cys His Thr Pro Glu Pro Thr Cys Pro Pro His

3065 3070 3075

Glu Phe Lys Cys Asp Asn Gly Arg Cys Ile Glu Met Met Lys Leu

3080 3085 3090

Cys Asn His Leu Asp Asp Cys Leu Asp Asn Ser Asp Glu Lys Gly

3095 3100 3105

Cys Gly Ile Asn Glu Cys His Asp Pro Ser Ile Ser Gly Cys Asp

3110 3115 3120

His Asn Cys Thr Asp Thr Leu Thr Ser Phe Tyr Cys Ser Cys Arg

3125 3130 3135

Pro Gly Tyr Lys Leu Met Ser Asp Lys Arg Thr Cys Val Asp Ile

3140 3145 3150

Asp Glu Cys Thr Glu Met Pro Phe Val Cys Ser Gln Lys Cys Glu

3155 3160 3165

Asn Val Ile Gly Ser Tyr Ile Cys Lys Cys Ala Pro Gly Tyr Leu

3170 3175 3180

Arg Glu Pro Asp Gly Lys Thr Cys Arg Gln Asn Ser Asn Ile Glu

3185 3190 3195

Pro Tyr Leu Ile Phe Ser Asn Arg Tyr Tyr Leu Arg Asn Leu Thr

3200 3205 3210

Ile Asp Gly Tyr Phe Tyr Ser Leu Ile Leu Glu Gly Leu Asp Asn

3215 3220 3225

Val Val Ala Leu Asp Phe Asp Arg Val Glu Lys Arg Leu Tyr Trp

3230 3235 3240

Ile Asp Thr Gln Arg Gln Val Ile Glu Arg Met Phe Leu Asn Lys

3245 3250 3255

Thr Asn Lys Glu Thr Ile Ile Asn His Arg Leu Pro Ala Ala Glu

3260 3265 3270

Ser Leu Ala Val Asp Trp Val Ser Arg Lys Leu Tyr Trp Leu Asp

3275 3280 3285

Ala Arg Leu Asp Gly Leu Phe Val Ser Asp Leu Asn Gly Gly His

3290 3295 3300

Arg Arg Met Leu Ala Gln His Cys Val Asp Ala Asn Asn Thr Phe

3305 3310 3315

Cys Phe Asp Asn Pro Arg Gly Leu Ala Leu His Pro Gln Tyr Gly

3320 3325 3330

Tyr Leu Tyr Trp Ala Asp Trp Gly His Arg Ala Tyr Ile Gly Arg

3335 3340 3345

Val Gly Met Asp Gly Thr Asn Lys Ser Val Ile Ile Ser Thr Lys

3350 3355 3360

Leu Glu Trp Pro Asn Gly Ile Thr Ile Asp Tyr Thr Asn Asp Leu

3365 3370 3375

Leu Tyr Trp Ala Asp Ala His Leu Gly Tyr Ile Glu Tyr Ser Asp

3380 3385 3390

Leu Glu Gly His His Arg His Thr Val Tyr Asp Gly Ala Leu Pro

3395 3400 3405

His Pro Phe Ala Ile Thr Ile Phe Glu Asp Thr Ile Tyr Trp Thr

3410 3415 3420

Asp Trp Asn Thr Arg Thr Val Glu Lys Gly Asn Lys Tyr Asp Gly

3425 3430 3435

Ser Asn Arg Gln Thr Leu Val Asn Thr Thr His Arg Pro Phe Asp

3440 3445 3450

Ile His Val Tyr His Pro Tyr Arg Gln Pro Ile Val Ser Asn Pro

3455 3460 3465

Cys Gly Thr Asn Asn Gly Gly Cys Ser His Leu Cys Leu Ile Lys

3470 3475 3480

Pro Gly Gly Lys Gly Phe Thr Cys Glu Cys Pro Asp Asp Phe Arg

3485 3490 3495

Thr Leu Gln Leu Ser Gly Ser Thr Tyr Cys Met Pro Met Cys Ser

3500 3505 3510

Ser Thr Gln Phe Leu Cys Ala Asn Asn Glu Lys Cys Ile Pro Ile

3515 3520 3525

Trp Trp Lys Cys Asp Gly Gln Lys Asp Cys Ser Asp Gly Ser Asp

3530 3535 3540

Glu Leu Ala Leu Cys Pro Gln Arg Phe Cys Arg Leu Gly Gln Phe

3545 3550 3555

Gln Cys Ser Asp Gly Asn Cys Thr Ser Pro Gln Thr Leu Cys Asn

3560 3565 3570

Ala His Gln Asn Cys Pro Asp Gly Ser Asp Glu Asp Arg Leu Leu

3575 3580 3585

Cys Glu Asn His His Cys Asp Ser Asn Glu Trp Gln Cys Ala Asn

3590 3595 3600

Lys Arg Cys Ile Pro Glu Ser Trp Gln Cys Asp Thr Phe Asn Asp

3605 3610 3615

Cys Glu Asp Asn Ser Asp Glu Asp Ser Ser His Cys Ala Ser Arg

3620 3625 3630

Thr Cys Arg Pro Gly Gln Phe Arg Cys Ala Asn Gly Arg Cys Ile

3635 3640 3645

Pro Gln Ala Trp Lys Cys Asp Val Asp Asn Asp Cys Gly Asp His

3650 3655 3660

Ser Asp Glu Pro Ile Glu Glu Cys Met Ser Ser Ala His Leu Cys

3665 3670 3675

Asp Asn Phe Thr Glu Phe Ser Cys Lys Thr Asn Tyr Arg Cys Ile

3680 3685 3690

Pro Lys Trp Ala Val Cys Asn Gly Val Asp Asp Cys Arg Asp Asn

3695 3700 3705

Ser Asp Glu Gln Gly Cys Glu Glu Arg Thr Cys His Pro Val Gly

3710 3715 3720

Asp Phe Arg Cys Lys Asn His His Cys Ile Pro Leu Arg Trp Gln

3725 3730 3735

Cys Asp Gly Gln Asn Asp Cys Gly Asp Asn Ser Asp Glu Glu Asn

3740 3745 3750

Cys Ala Pro Arg Glu Cys Thr Glu Ser Glu Phe Arg Cys Val Asn

3755 3760 3765

Gln Gln Cys Ile Pro Ser Arg Trp Ile Cys Asp His Tyr Asn Asp

3770 3775 3780

Cys Gly Asp Asn Ser Asp Glu Arg Asp Cys Glu Met Arg Thr Cys

3785 3790 3795

His Pro Glu Tyr Phe Gln Cys Thr Ser Gly His Cys Val His Ser

3800 3805 3810

Glu Leu Lys Cys Asp Gly Ser Ala Asp Cys Leu Asp Ala Ser Asp

3815 3820 3825

Glu Ala Asp Cys Pro Thr Arg Phe Pro Asp Gly Ala Tyr Cys Gln

3830 3835 3840

Ala Thr Met Phe Glu Cys Lys Asn His Val Cys Ile Pro Pro Tyr

3845 3850 3855

Trp Lys Cys Asp Gly Asp Asp Asp Cys Gly Asp Gly Ser Asp Glu

3860 3865 3870

Glu Leu His Leu Cys Leu Asp Val Pro Cys Asn Ser Pro Asn Arg

3875 3880 3885

Phe Arg Cys Asp Asn Asn Arg Cys Ile Tyr Ser His Glu Val Cys

3890 3895 3900

Asn Gly Val Asp Asp Cys Gly Asp Gly Thr Asp Glu Thr Glu Glu

3905 3910 3915

His Cys Arg Lys Pro Thr Pro Lys Pro Cys Thr Glu Tyr Glu Tyr

3920 3925 3930

Lys Cys Gly Asn Gly His Cys Ile Pro His Asp Asn Val Cys Asp

3935 3940 3945

Asp Ala Asp Asp Cys Gly Asp Trp Ser Asp Glu Leu Gly Cys Asn

3950 3955 3960

Lys Gly Lys Glu Arg Thr Cys Ala Glu Asn Ile Cys Glu Gln Asn

3965 3970 3975

Cys Thr Gln Leu Asn Glu Gly Gly Phe Ile Cys Ser Cys Thr Ala

3980 3985 3990

Gly Phe Glu Thr Asn Val Phe Asp Arg Thr Ser Cys Leu Asp Ile

3995 4000 4005

Asn Glu Cys Glu Gln Phe Gly Thr Cys Pro Gln His Cys Arg Asn

4010 4015 4020

Thr Lys Gly Ser Tyr Glu Cys Val Cys Ala Asp Gly Phe Thr Ser

4025 4030 4035

Met Ser Asp Arg Pro Gly Lys Arg Cys Ala Ala Glu Gly Ser Ser

4040 4045 4050

Pro Leu Leu Leu Leu Pro Asp Asn Val Arg Ile Arg Lys Tyr Asn

4055 4060 4065

Leu Ser Ser Glu Arg Phe Ser Glu Tyr Leu Gln Asp Glu Glu Tyr

4070 4075 4080

Ile Gln Ala Val Asp Tyr Asp Trp Asp Pro Lys Asp Ile Gly Leu

4085 4090 4095

Ser Val Val Tyr Tyr Thr Val Arg Gly Glu Gly Ser Arg Phe Gly

4100 4105 4110

Ala Ile Lys Arg Ala Tyr Ile Pro Asn Phe Glu Ser Gly Arg Asn

4115 4120 4125

Asn Leu Val Gln Glu Val Asp Leu Lys Leu Lys Tyr Val Met Gln

4130 4135 4140

Pro Asp Gly Ile Ala Val Asp Trp Val Gly Arg His Ile Tyr Trp

4145 4150 4155

Ser Asp Val Lys Asn Lys Arg Ile Glu Val Ala Lys Leu Asp Gly

4160 4165 4170

Arg Tyr Arg Lys Trp Leu Ile Ser Thr Asp Leu Asp Gln Pro Ala

4175 4180 4185

Ala Ile Ala Val Asn Pro Lys Leu Gly Leu Met Phe Trp Thr Asp

4190 4195 4200

Trp Gly Lys Glu Pro Lys Ile Glu Ser Ala Trp Met Asn Gly Glu

4205 4210 4215

Asp Arg Asn Ile Leu Val Phe Glu Asp Leu Gly Trp Pro Thr Gly

4220 4225 4230

Leu Ser Ile Asp Tyr Leu Asn Asn Asp Arg Ile Tyr Trp Ser Asp

4235 4240 4245

Phe Lys Glu Asp Val Ile Glu Thr Ile Lys Tyr Asp Gly Thr Asp

4250 4255 4260

Arg Arg Val Ile Ala Lys Glu Ala Met Asn Pro Tyr Ser Leu Asp

4265 4270 4275

Ile Phe Glu Asp Gln Leu Tyr Trp Ile Ser Lys Glu Lys Gly Glu

4280 4285 4290

Val Trp Lys Gln Asn Lys Phe Gly Gln Gly Lys Lys Glu Lys Thr

4295 4300 4305

Leu Val Val Asn Pro Trp Leu Thr Gln Val Arg Ile Phe His Gln

4310 4315 4320

Leu Arg Tyr Asn Lys Ser Val Pro Asn Leu Cys Lys Gln Ile Cys

4325 4330 4335

Ser His Leu Cys Leu Leu Arg Pro Gly Gly Tyr Ser Cys Ala Cys

4340 4345 4350

Pro Gln Gly Ser Ser Phe Ile Glu Gly Ser Thr Thr Glu Cys Asp

4355 4360 4365

Ala Ala Ile Glu Leu Pro Ile Asn Leu Pro Pro Pro Cys Arg Cys

4370 4375 4380

Met His Gly Gly Asn Cys Tyr Phe Asp Glu Thr Asp Leu Pro Lys

4385 4390 4395

Cys Lys Cys Pro Ser Gly Tyr Thr Gly Lys Tyr Cys Glu Met Ala

4400 4405 4410

Phe Ser Lys Gly Ile Ser Pro Gly Thr Thr Ala Val Ala Val Leu

4415 4420 4425

Leu Thr Ile Leu Leu Ile Val Val Ile Gly Ala Leu Ala Ile Ala

4430 4435 4440

Gly Phe Phe His Tyr Arg Arg Thr Gly Ser Leu Leu Pro Ala Leu

4445 4450 4455

Pro Lys Leu Pro Ser Leu Ser Ser Leu Val Lys Pro Ser Glu Asn

4460 4465 4470

Gly Asn Gly Val Thr Phe Arg Ser Gly Ala Asp Leu Asn Met Asp

4475 4480 4485

Ile Gly Val Ser Gly Phe Gly Pro Glu Thr Ala Ile Asp Arg Ser

4490 4495 4500

Met Ala Met Ser Glu Asp Phe Val Met Glu Met Gly Lys Gln Pro

4505 4510 4515

Ile Ile Phe Glu Asn Pro Met Tyr Ser Ala Arg Asp Ser Ala Val

4520 4525 4530

Lys Val Val Gln Pro Ile Gln Val Thr Val Ser Glu Asn Val Asp

4535 4540 4545

Asn Lys Asn Tyr Gly Ser Pro Ile Asn Pro Ser Glu Ile Val Pro

4550 4555 4560

Glu Thr Asn Pro Thr Ser Pro Ala Ala Asp Gly Thr Gln Val Thr

4565 4570 4575

Lys Trp Asn Leu Phe Lys Arg Lys Ser Lys Gln Thr Thr Asn Phe

4580 4585 4590

Glu Asn Pro Ile Tyr Ala Gln Met Glu Asn Glu Gln Lys Glu Ser

4595 4600 4605

Val Ala Ala Thr Pro Pro Pro Ser Pro Ser Leu Pro Ala Lys Pro

4610 4615 4620

Lys Pro Pro Ser Arg Arg Asp Pro Thr Pro Thr Tyr Ser Ala Thr

4625 4630 4635

Glu Asp Thr Phe Lys Asp Thr Ala Asn Leu Val Lys Glu Asp Ser

4640 4645 4650

Glu Val

4655

<210> 941

<211> 21

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 941

cctaaggtta agtcgccctc g 21

<210> 942

<211> 21

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 942

cgagggcgac ttaaccttag g 21

<210> 943

<211> 21

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 943

ccctcagaga cctgagctct t 21

<210> 944

<211> 21

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 944

aagagctcag gtctctgagg g 21

<210> 945

<211> 21

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 945

cctgtaataa acactactct t 21

<210> 946

<211> 21

<212> DNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 946

aagagtagtg tttattacag g 21

<210> 947

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 947

ccuaagguua agucgcccuc g 21

<210> 948

<211> 19

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 948

ugguuuacau guuguguga 19

<210> 949

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 949

gggcucuagg uuuggugcua ucaaa 25

<210> 950

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 950

ggacugauag gagagucauu gcaaa 25

<210> 951

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 951

ccuguaauaa acacuacucu u 21

<210> 952

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 952

ccuucuauga accuggccuu a 21

<210> 953

<211> 19

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 953

gugauuugau uauacggca 19

<210> 954

<211> 19

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 954

ccucaaaugg cuguagcaa 19

<210> 955

<211> 25

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 955

gaacugacaa gaaacugcgc aacug 25

<210> 956

<211> 21

<212> RNA

<213> Artificial sequence

<220>

<223> description of artificial sequences: synthesis of

Oligonucleotides

<400> 956

cccucagaga ccugagcucu u 21