阅读说明：本技术 纤毛疾病的治疗 (Treatment of cilia disease ) 是由 C·鲁道夫 V·克雷茨施曼 R·库比什-多曼 C·多曼 J·盖革 M·阿内嘉 L·威斯 于 2020-02-13 设计创作，主要内容包括：本公开提供了一种用于治疗患有纤毛疾病的受试者的纤毛疾病的包含多核糖核苷酸的药物组合物,其中多核糖核苷酸编码其缺陷与所述纤毛疾病相关的蛋白的功能性版本,并且其中当受试者表现出呼吸系统的炎症时将所述药物组合物施用于所述受试者的呼吸系统。进一步地,本公开涉及用于分析多核糖核苷酸对纤毛形成的作用的方法,其中所述多核糖核苷酸编码参与纤毛形成和/或纤毛形成所需的蛋白。(The present disclosure provides a pharmaceutical composition comprising a polyribonucleotide for treating a cilial disease in a subject suffering from the cilial disease, wherein the polyribonucleotide encodes a functional version of a protein whose defect is associated with the cilial disease, and wherein the pharmaceutical composition is administered to the respiratory system of the subject when the subject exhibits inflammation of the respiratory system. Further, the present disclosure relates to methods for analyzing the effect of polyribonucleotides on cilia formation, wherein the polyribonucleotides encode proteins required for participation in cilia formation and/or cilia formation.)

1.A pharmaceutical composition comprising a polyribonucleotide for treating a cilial disease in a subject suffering from a cilial disease, wherein the polyribonucleotide encodes a functional version of a protein whose defect is associated with the cilial disease, and wherein the pharmaceutical composition is administered to the respiratory system of the patient when the patient exhibits inflammation of the respiratory system.

2. The pharmaceutical composition comprising polyribonucleotides for use in treating a cilial disease according to any of the preceding claims, wherein the cilial disease is Primary Ciliary Dyskinesia (PCD).

3. The pharmaceutical composition comprising polyribonucleotides for use in treating a cilial disease according to any of the preceding claims, wherein the cilial disease is associated with a defect in the 40(CCDC40) protein comprising a coiled-coil domain and/or with a defect in the 39(CCDC39) protein comprising a coiled-coil domain.

4. The pharmaceutical composition comprising polyribonucleotides for use in the treatment of a cilial disease according to any of the preceding claims, wherein the presence or absence of inflammation of the respiratory system of a subject suffering from a cilial disease is determined by analyzing a blood sample and/or by analyzing the amount of nitric oxide exhaled.

5. The pharmaceutical composition comprising polyribonucleotides for use in the treatment of cilial disease according to any of the preceding claims, wherein administration of the pharmaceutical composition comprises administration using a nasal spray and/or nebulizer and/or by inhalation.

6. The pharmaceutical composition comprising polyribonucleotides for use in the treatment of cilia disease according to any of the preceding claims, wherein said pharmaceutical composition is administered at least once per week and/or for at least 4 weeks.

7. The pharmaceutical composition comprising polyribonucleotides for use in the treatment of ciliary disease according to any of the preceding claims, wherein said pharmaceutical composition further comprises N-acetylcysteine (NAC) and/or a hypertonic solution comprising sodium chloride.

8. The pharmaceutical composition comprising polyribonucleotides for use in the treatment of a cilial disease according to any of the preceding claims, wherein the pharmaceutical composition further comprises a polyribonucleotide encoding a cell cycle associated with differentiation of the fibrilia and DNA synthesis (MCIDAS) protein, and/or wherein the pharmaceutical composition is a first pharmaceutical composition to be administered together with a second pharmaceutical composition comprising a polyribonucleotide encoding an MCIDAS protein.

9. The pharmaceutical composition comprising polyribonucleotides for use in the treatment of cilial disease according to any of the preceding claims, wherein said pharmaceutical composition further comprises a lipid-like (lipidoid) having the structure shown in formula (V):

10. a pharmaceutical composition comprising a polyribonucleotide encoding a protein whose defect is associated with ciliary disease and N-acetylcysteine (NAC), a hypertonic solution comprising sodium chloride, and/or an LF92 preparation.

11. A method for analyzing the effect of polyribonucleotides on cilia formation, wherein the polyribonucleotides encode proteins required for participation in cilia formation and/or cilia formation, the method comprising the steps of:

(a) obtaining a nasal brush of a subject having a cilial disease, the nasal brush comprising undifferentiated basal cells and differentiated ciliated cells,

(b) culturing said cells obtained from step (a) as a submerged cell culture for obtaining undifferentiated basal cells and dedifferentiated ciliated cells,

(c) culturing the undifferentiated basal cells and the dedifferentiated ciliated cells obtained from step (b) as a gas-liquid interface cell culture and performing gas lift,

(d) transfecting the cells obtained from step (c) with a polyribonucleotide encoding a protein involved in cilia formation and/or cilia formation,

(e) culturing said transfected cells obtained from step (d) for obtaining differentiated ciliated cells, and

(f) the effect of the polyribonucleotide on cilia formation is determined using lactate dehydrogenase measurement, a NucGreen assay, high speed video microscopy, cilia beat frequency measurement, mucociliary clearance assay, and/or immunofluorescence staining.

12. The method of claim 11, wherein the cells are transfected within 0 to 48 hours after the gas lift is performed in step (c).

13. A method according to claim 11 or 12, wherein the cell is transfected with a polyribonucleotide encoding a protein involved in cilia formation and/or a protein required for cilia formation using a lipid having a structure according to formula (V).

14. The method of any one of claims 11 to 13, wherein the cells are cultured in steps (b) to (e) using medium G.

15. The method according to any one of claims 11 to 14, wherein the nasal brush further comprises fibroblasts, and wherein the growth of the fibroblasts is inhibited in steps (b) to (e).