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    • 93. 发明授权
    • Selectively replicating viral vectors
    • 选择性复制病毒载体
    • US08133481B2
    • 2012-03-13
    • US12706134
    • 2010-02-16
    • Muralidhara RamachandraPaul W. Shabram
    • Muralidhara RamachandraPaul W. Shabram
    • A01N63/00A61K35/713A61K48/00C07H21/04C12N15/00C12N15/12C12N15/34
    • C12N15/86A61K48/00C12N2710/10332C12N2710/10343C12N2830/00C12N2830/001C12N2830/15
    • The present invention provides recombinant viruses which replicate the viral genome selectively in response to the intracellular conditions of the target cell through the use a pathway-responsive promoter which substantially inhibits viral replication in the host cell based on the phenotypic or genotypic of the infected cell. In the target cell, the promoter element of the pathway-responsive promoter is inactive and thus the virus is permitted to replicate. This results in: (1) killing the cells by natural lytic nature of the virus, and/or (2) provides a therapeutic dose of a transgene product (amplified in comparison to replication incompetent vectors) to the target cell, and (3) producing a localized concentration of the virus facilitating the infection of surrounding cells to the recombinant virus. The invention further provides therapeutic and diagnostic methods of use of the vectors, pharmaceutical formulations comprising the vectors, methods of making the vectors and transformed cells comprising the vectors.
    • 本发明提供了通过使用基于感染细胞的表型或基因型基本上抑制宿主细胞中的病毒复制的途径反应性启动子来响应于靶细胞的细胞内条件而选择性复制病毒基因的重组病毒。 在靶细胞中,途径反应性启动子的启动子元件是无活性的,因此病毒被允许复制。 这导致:(1)通过病毒的天然裂解性质杀死细胞,和/或(2)向靶细胞提供治疗剂量的转基因产物(与复制无能载体相比扩增),和(3) 产生该病毒的局部浓度,促进周围细胞感染重组病毒。 本发明还提供了使用载体的治疗和诊断方法,包含载体的药物制剂,制备载体的方法和包含载体的转化细胞。