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    Design of novel highly efficient HIV based packaging systems for gene therapy
    9.
    发明授权
    Design of novel highly efficient HIV based packaging systems for gene therapy 失效
    用于基因治疗的新颖高效的基于HIV的包装系统的设计

    公开(公告)号：US06323019B1

    公开(公告)日：2001-11-27

    申请号：US09131684

    申请日：1998-08-10

    申请人： Pierre Corbeau ,  Gunter Kraus ,  Flossie Wong-Staal

    发明人： Pierre Corbeau ,  Gunter Kraus ,  Flossie Wong-Staal

    IPC分类号： C12N1564

    CPC分类号： C12N7/00 ,  A61K38/00 ,  A61K48/00 ,  C07K14/005 ,  C12N15/86 ,  C12N2740/16052 ,  C12N2740/16122

    摘要： By transducing cells with an HIV-1-MN molecular clone deleted in the major packaging sequence, a stable HIV-1 packaging cell line, &psgr;422 was produced. &psgr;422 cells form syncytia with CD4 positive cells, correctly express HIV-1 structural proteins, and produce large amount of mature particles with normal RT activity. These particles are not infectious. When stably transfected with an HIV-based retroviral vector, the &psgr;422 cell line produces hybrid virions capable of transducing CD4 positive cells with high efficiency (e.g., 105 cells/ml). The availability of this stable, noninfectious HIV-1 packaging cell line capable of generating high titer HIV vectors enables the use of HIV-1 based nucleic acids delivery systems, for example, in gene therapy. An HIV-2 based vector is packaged by the packaging cell lines, demonstrating that HIV-2 cell transformation vectors are packaged by the packaging cell line. HIV based vectors packaged by the high efficiency cell lines are shown to have anti-HIV activity per se.

    摘要翻译： 通过在主要包装序列中缺失的HIV-1-MN分子克隆转导细胞，产生稳定的HIV-1包装细胞系psi422。 psi422细胞与CD4阳性细胞形成合胞体，正确表达HIV-1结构蛋白，并产生大量具有正常RT活性的成熟颗粒。 这些颗粒不感染。 当用HIV-型逆转录病毒载体稳定转染时，psi422细胞系产生能够以高效率（例如，105个细胞/ ml）转导CD4阳性细胞的杂合病毒体。 能够产生高滴度的HIV载体的这种稳定的，非感染性的HIV-1包装细胞系的可用性使得能够使用基于HIV-1的核酸递送系统，例如在基因治疗中。 通过包装细胞系包装基于HIV-2的载体，证明HIV-2细胞转化载体被包装细胞系包装。 由高效细胞系包装的基于HIV的载体显示出具有抗HIV活性本身。