IMPROVED PACKAGING CELLS FOR RECOMBINANT RETROVIRUSES

描述：(改编自申请人的摘要)对使用至关重要 逆转录病毒介导的基因转移用于体细胞人的方案 基因治疗是一种高效、安全的体外基因转移方法。效率 逆转录病毒介导的转导由几个因素决定，包括 病毒制剂的质量以及接受者的特性 手机。细胞表面空置病毒受体的丰度 可能会限制基因转移的效率。所有重组逆转录病毒 目前可用于人类基因转移的是基于两性的 被特定的、特征不佳的细胞内化的菌株 表面受体。该项目的总体目标是创建 能够显著改善基因转移的重组逆转录病毒 进入人类细胞。第一阶段的研究将尝试产生重组 基于内化的异嗜性病毒株的逆转录病毒 通过一种与两性病毒不同的受体。这个 异嗜性重组人细胞转导效率的研究 逆转录病毒将与两性病毒的结果进行比较。阶段 II研究将试图进一步提高逆转录病毒的效率 通过创建病毒包装细胞系来介导基因转移 过度表达病毒粒子形成所必需的蛋白质成分。

DESCRIPTION: (Adapted from the applicant's abstract) Critical to the use of retroviral-mediated gene transfer for protocols of somatic cell human gene therapy is efficient and safe gene transfer in vitro. Efficiency of retrovirus mediated transduction is determined by several factors including the quality of virus preparation as well as properties of the recipient cell. The abundance of unoccupied virus receptor on the surface of cells may limit the efficiency of gene transfer. All recombinant retroviruses currently available for human gene transfer are based on an amphotropic strain that is internalized by a specific, poorly characterized, cell surface receptor. The overall goal of this project is to create recombinant retroviruses capable of substantially improved gene transfer into human cells. Phase I studies will attempt to generate recombinant retroviruses based on a xenotropic strain of virus which is internalized via a receptor distinct from that used by amphotropic virus. The efficiency of transduction of human cells by the xenotropic recombinant retrovirus will be compared to results with amphotropic based virus. Phase II studies will attempt to further improve the efficiency of retrovirus mediated gene transfer by creating virus packaging cell lines that overexpress the protein components necessary for virion formation.