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    • 1. 发明授权
    • Development of viruses resistant to inactivation by the human complement system
    • 开发抗人类补体系统灭活的病毒
    • US06475756B1
    • 2002-11-05
    • US09554838
    • 2000-07-21
    • Dagmar WirthDirk SpitzerHansjoerg Hauser
    • Dagmar WirthDirk SpitzerHansjoerg Hauser
    • C12P2104
    • C07K14/005A61K48/00C07K14/70596C07K2319/00C12N15/86C12N2740/13022C12N2740/13043C12N2740/13045C12N2740/13052C12N2810/60C12N2810/855
    • Murine retroviruses are the most important transfer systems for human gene therapy. However, their application is currently limited. One of the major restrictions both for an application in vivo resides in the problem that this virus type is sensitive to inactivation by human complement factors. Our invention overcomes this limitation. We have modified murine recombinant retroviruses in a way that they are resistant to human complement factors. This was achieved by genetic modification of the retroviral surface protein env which is responsible for receptor interaction: the receptor interacting domain of env was fused to catalytically active domains of human complement inactivation factors. These modified env were expressed in complement-sensitive cells and specifically integrated into virus particles. By this strategy cells and viruses are generated that are fully resistant to complement attack. Thus, this strategy provides a tool for establishment of complement resistant cells and generation of viruses for in vivo gene therapy.
    • 鼠逆转录病毒是人类基因治疗最重要的转移系统。 但是,它们的应用目前是有限的。 在体内应用的主要限制之一在于这种病毒类型对人补体因子的失活敏感的问题。 我们的发明克服了这个限制。 我们已经修改了鼠重组逆转录病毒,使其具有抗人补体因子的作用。 这是通过负责受体相互作用的逆转录病毒表面蛋白env的遗传修饰实现的:env的受体相互作用结构域融合到人补体失活因子的催化活性结构域。 这些修饰的env在补体敏感细胞中表达并且特异性整合到病毒颗粒中。 通过这种策略,产生完全抵抗补体攻击的细胞和病毒。 因此,该策略提供了建立补体抗性细胞和产生用于体内基因治疗的病毒的工具。