多倍体腺相关病毒载体及其制备和使用方法

文档序号:1509966 发布日期:2020-02-07 浏览:24次 >En<

阅读说明:本技术 多倍体腺相关病毒载体及其制备和使用方法 (Polyploid adeno-associated virus vector and preparation and use method thereof ) 是由 R.J.萨穆尔斯基 C.李 于 2018-03-15 设计创作,主要内容包括:本发明提供了多倍体腺相关病毒(AAV)衣壳,其中所述衣壳包含衣壳蛋白VP1,其中所述衣壳蛋白VP1来自一种或多于一种第一AAV血清型,其中所述衣壳蛋白VP2来自一种或多于一种第一AAV血清型,以及衣壳蛋白VP3,其中所述衣壳蛋白VP3来自一种或多于一种第二AAV血清型,并且其中在任何组合中所述第一AAV血清型中的至少一种不同于所述第二AAV血清型中的至少一种,并且不同于所述第三AAV血清型中的至少一种。(The present invention provides a polyploid adeno-associated virus (AAV) capsid, wherein the capsid comprises a capsid protein VP1, wherein the capsid protein VP1 is from one or more than one first AAV serotype, wherein the capsid protein VP2 is from one or more than one first AAV serotype, and a capsid protein VP3, wherein the capsid protein VP3 is from one or more than one second AAV serotype, and wherein at least one of the first AAV serotypes is different from at least one of the second AAV serotypes, and different from at least one of the third AAV serotypes in any combination.)

具体实施方式

中所述的数目范围和值尽可能精确地报告。然而,任何数目范围或值固有地含有必然起因于其分别测试测量中发现的标准差的某些误差。在本文中值的数目范围的叙述仅预期充当个别提及落入该范围内的每个分开数值的简写方法。除非本文另有说明,否则数目范围的每个个别值掺入本说明书内,如同它在本文中个别叙述一样。

除非本文另有说明或上下文明显矛盾,否则本文所述的所有方法可以以任何合适的次序执行。本文提供的任何和所有实例或示例性语言(例如,“诸如”)的使用仅预期更好地示出本发明,而不是对请求保护的本发明的范围造成限制。本说明书中的任何语言都不应解释为指示对本发明的实践必需的任何未请求保护的要素。

本文公开的具体实施方案可以使用语言由……组成或基本上由……组成在权利要求中进一步限制。当在权利要求中使用时,无论是如提交的还是按修饰添加,过渡术语“由……组成”排除权利要求中未指定的任何要素、步骤或成分。过渡术语“基本上由……组成”将权利要求的范围限制在指定的材料或步骤,以及不会在材料上影响基本和新型特征的那些。如此请求保护的本发明的实施方案在本文中固有地或明确地描述且实现。

本说明书中引用且鉴定的所有专利、专利出版物及其它出版物都个别地和明确地整体引入本文作为参考,用于描述和公开例如可以与本发明结合使用的此类出版物中描述的组合物和方法的目的。提供这些出版物仅由于其公开内容在本申请的提交日期前。在这点上不应解释为承认由于本发明或由于任何其他原因,本发明人有资格先于此类公开内容。关于日期的所有声明或关于这些文件内容的表达基于申请人可获得的信息,并且不构成关于这些文件的日期或内容正确性的任何承认。

表1

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表2:氨基酸残基和缩写

Figure 584664DEST_PATH_IMAGE009

表3

Figure 338993DEST_PATH_IMAGE010

表4:

Figure 889054DEST_PATH_IMAGE011

表5:关于AAV8结合血清蛋白质的MS结果

Figure 412439DEST_PATH_IMAGE012

表5(续):

Figure 842284DEST_PATH_IMAGE013

*ND指示在对照组中未检测到蛋白质。

表6:关于AAV9结合血清蛋白质的MS结果

Figure 146226DEST_PATH_IMAGE014

Figure 64820DEST_PATH_IMAGE016

*ND指示在对照组中未检测到蛋白质。

表7:结合AAV9用于增加血管通透性的潜在血清蛋白质

*ND指示在对照组中未检测到蛋白质。

表8

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表9:VIPR对体内抗原呈递的作用

Figure 516378DEST_PATH_IMAGE019

表10:关于三倍体病毒AAV2/8的中和抗体滴度和交叉反应性

Figure 76672DEST_PATH_IMAGE020

表11:关于单倍体病毒AAV2/8/9的中和抗体滴度和交叉反应性

Figure 848319DEST_PATH_IMAGE021

Figure 798957DEST_PATH_IMAGE022

Figure 846996DEST_PATH_IMAGE024

Figure 789544DEST_PATH_IMAGE025

Figure 289796DEST_PATH_IMAGE026

Figure 710413DEST_PATH_IMAGE027

Figure 182982DEST_PATH_IMAGE028

Figure 608016DEST_PATH_IMAGE029

Figure 533247DEST_PATH_IMAGE030

Figure 757555DEST_PATH_IMAGE031

Figure 881369DEST_PATH_IMAGE032

Figure 165720DEST_PATH_IMAGE033

Figure 578246DEST_PATH_IMAGE034

Figure 419295DEST_PATH_IMAGE035

Figure 600877DEST_PATH_IMAGE036

Figure 318800DEST_PATH_IMAGE039

Figure 620469DEST_PATH_IMAGE040

Figure 295557DEST_PATH_IMAGE041

Figure 682676DEST_PATH_IMAGE042

Figure 52478DEST_PATH_IMAGE043

Figure 5390DEST_PATH_IMAGE044

Figure 802445DEST_PATH_IMAGE045

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