High efficiency retroviral vectors that contain none of viral coding sequences
    1.
    发明授权
    High efficiency retroviral vectors that contain none of viral coding sequences 有权
    不含病毒编码序列的高效率逆转录病毒载体

    公开(公告)号:US06451595B1

    公开(公告)日:2002-09-17

    申请号:US09463067

    申请日:2000-01-14

    IPC分类号: C12N15867

    摘要: The present invention relates to improved retroviral vectors for gene therapy. In this invention, retroviral vectors with higher safety and efficiency are constructed from MLV-based starting vectors, MON and MIN. The improved vectors have the following features: 1) sequences corresponding to MLV-derived pol gene are completely deleted in the vectors, avoiding homologous recombination which has been a baffling problem in conventional retroviral vectors, 2) a heterologous intron, splicing acceptor and/or non-coding sequence are/is inserted into the upstream position of a cloning site, maximizing the expression of a foreign gene through efficient splicing, 3) the vectors contain either the full-length U3 sequence of 5′ LTR or a strong heterologous promoter instead, permitting the abundant production of RNA, 4) either IRES (Internal Ribosomal Entry Site) or internal SV40 minimal promoter is inserted into the downstream position of cloning site, enabling the simultaneous expression of two or more foreign genes. Since the improved retroviral vectors of this invention turn out to be safe and to express the foreign gene efficiently, they are useful for gene therapy and the like.

    摘要翻译: 本发明涉及用于基因治疗的改良逆转录病毒载体。 在本发明中,具有更高安全性和效率的逆转录病毒载体由基于MLV的起始载体MON和MIN构建。 改进的载体具有以下特征:1)对应于MLV衍生的pol基因的序列在载体中完全缺失,避免了在常规逆转录病毒载体中已经成为障碍问题的同源重组,2)异源内含子,剪接受体和/或 非编码序列被插入到克隆位点的上游位置,通过有效剪接使外源基因的表达最大化,3)载体含有5'LTR的全长U3序列或者强异源启动子 ,允许大量产生RNA,4)将IRES(内部核糖体进入位点)或内部SV40最小启动子插入到克隆位点的下游位置,使得能够同时表达两个或多个外源基因。 由于本发明改良的逆转录病毒载体是安全的并有效表达外源基因,所以它们可用于基因治疗等。