Stable retrovirus and methods of use
    1.
    发明授权
    Stable retrovirus and methods of use 失效
    稳定的逆转录病毒及使用方法

    公开(公告)号:US07485446B2

    公开(公告)日:2009-02-03

    申请号:US11677110

    申请日:2007-02-21

    摘要: The present invention is a mutant retroviral protease which confers an increase in retroviral stability. Retroviruses expressing the instant mutant retroviral protease exhibit at least a 2-fold increase in infectivity half-life as compared to wild-type retrovirus. Unexpectedly, a Gly119Glu mutation in the protease enhances retroviral stability in the presence of various wild-type envelope proteins including wild-type amphotropic, ecotropic and 10A1 murine leukemia viruses. The improved stability of the mutant retrovirus leads to more facile virus production and enhanced infection efficiency.

    摘要翻译: 本发明是赋予逆转录病毒稳定性增加的突变型逆转录病毒蛋白酶。 与野生型逆转录病毒相比,表达本发明突变逆转录病毒蛋白酶的逆转录病毒体的感染性半衰期至少提高2倍。 意外的是,蛋白质中的Gly119Glu突变增强了在各种野生型包膜蛋白的存在下的逆转录病毒稳定性,包括野生型和平嗜性,嗜酸性和10A1鼠白血病病毒。 改进的突变逆转录病毒的稳定性导致更容易的病毒生产和增强的感染效率。

    Stable retrovirus and methods of use
    2.
    发明申请
    Stable retrovirus and methods of use 失效
    稳定的逆转录病毒及使用方法

    公开(公告)号:US20070196386A1

    公开(公告)日:2007-08-23

    申请号:US11677110

    申请日:2007-02-21

    IPC分类号: A61K39/395 A61K39/12

    摘要: The present invention is a mutant retroviral protease which confers an increase in retroviral stability. Retroviruses expressing the instant mutant retroviral protease exhibit at least a 2-fold increase in infectivity half-life as compared to wild-type retrovirus. Unexpectedly, a Gly119Glu mutation in the protease enhances retroviral stability in the presence of various wild-type envelope proteins including wild-type amphotropic, ecotropic and 10A1 murine leukemia viruses. The improved stability of the mutant retrovirus leads to more facile virus production and enhanced infection efficiency.

    摘要翻译: 本发明是赋予逆转录病毒稳定性增加的突变型逆转录病毒蛋白酶。 与野生型逆转录病毒相比,表达本发明突变逆转录病毒蛋白酶的逆转录病毒体的感染性半衰期至少提高2倍。 意外的是,蛋白质中的Gly119Glu突变增强了在各种野生型包膜蛋白的存在下的逆转录病毒稳定性,包括野生型和平嗜性,嗜酸性和10A1鼠白血病病毒。 改进的突变逆转录病毒的稳定性导致更容易的病毒生产和增强的感染效率。

    Cell delivery compositions
    4.
    发明授权
    Cell delivery compositions 失效
    细胞递送组合物

    公开(公告)号:US06692911B2

    公开(公告)日:2004-02-17

    申请号:US09251783

    申请日:1999-02-17

    IPC分类号: C12Q168

    摘要: The present invention provides improved cell delivery compositions. In particular, the invention provides biocompatible endosomolytic agents. In a preferred embodiment, the endosomolytic agents are also biodegradable and can be broken down within cells into components that the cells can either reuse or dispose of. Preferred endosomolytic agents include cationic polymers, particularly those comprised of biomolecules, such as histidine, polyhistidine, polylysine or any combination thereof. Other exemplary endosomolytic agents include, but are not limited to, other imidazole containing compounds such as vinylimidazole and histamine. More particularly preferred are those agents having multiple proton acceptor sites and acting as a “proton sponge”, disrupting the endosome by osmolytic action. In preferred embodiments, the endosomolytic agent comprises a plurality of proton acceptor sites having pKas within the range of 4 to 7, which endosomal lysing component is polycationic at pH 4. The present invention also contemplates the use of these endosomolytic agents as delivery agents by complexation with the desired compound to be delivered. Thus, the present invention also acts as a cell delivery system comprising an endosomolytic agent, a delivery agent, and a compound to be delivered.

    摘要翻译: 本发明提供了改进的细胞递送组合物。 特别地,本发明提供生物相容的内体细胞溶解剂。 在优选的实施方案中,内体细胞溶解剂也是可生物降解的,并且可以在细胞内分解成细胞可以再利用或处置的组分。 优选的内细胞分解剂包括阳离子聚合物,特别是由生物分子如组氨酸,聚组氨酸,聚赖氨酸或其任何组合组成的聚合物。 其它示例性的内细胞溶解剂包括但不限于其它含咪唑的化合物如乙烯基咪唑和组胺。 更特别优选的是具有多个质子受体位点并用作“质子海绵”的那些试剂,通过渗透作用破坏内体。 在优选的实施方案中,内体细胞溶解剂包含多个质子受体位点,其pKas在4至7范围内,该内体裂解组分在pH 4下是阳离子的。本发明还考虑通过络合使用这些内分泌溶剂作为递送剂 与期望的化合物被输送。 因此,本发明还用作包含内体细胞分解剂,递送剂和待递送化合物的细胞递送系统。