METHOD AND COMPOSITION FOR CREATING CONDITIONAL LETHALITY FOR VIRUS MUTANTS AND FOR ELIMINATING THE VIABILITY OF AN EUKARYOTIC CELL
    3.
    发明申请
    METHOD AND COMPOSITION FOR CREATING CONDITIONAL LETHALITY FOR VIRUS MUTANTS AND FOR ELIMINATING THE VIABILITY OF AN EUKARYOTIC CELL 审中-公开
    用于为病毒突变体创造条件性遗传和消除真核细胞的可能性的方法和组合物

    公开(公告)号:US20120282225A1

    公开(公告)日:2012-11-08

    申请号:US13500010

    申请日:2010-09-13

    摘要: Viral vectors are potential tools for eliminating the viability of eukaryotic cells in anti-cancer therapies since they can efficiently destroy the cancer cells and trigger an immune response against tumours. Typically viruses are not specific to cancer cells and all methods known in art aiming to the construction of cancer-specific viruses suffer from serious problems. The present invention presents a universal method to overcome these problems and is usable for any DNA virus replicating in nucleus or for any layered vector of RNA viruses. In this method the viral gene expression and/or replication will be blocked by the introduction of one or more aberrantly spliced introns into crucial gene expression units of the virus or vector. Lethal effect of these mutations is reverted in a controlled manner by the delivery of splice-switch oligonucleotide (s) correcting the introduced defects and restoring the biological functionality of the virus or vector, including cytolytic properties.

    摘要翻译: 病毒载体是消除抗癌治疗中真核细胞活力的潜在工具,因为它们可以有效地破坏癌细胞并引发针对肿瘤的免疫应答。 通常,病毒对癌细胞不是特异性的,并且用于构建癌症特异性病毒的艺术中已知的所有方法都遭受严重问题。 本发明提出了克服这些问题的通用方法,并且可用于在核中或任何分层RNA病毒载体中复制的任何DNA病毒。 在该方法中,通过将一个或多个异常剪接的内含子引入病毒或载体的关键基因表达单元中,病毒基因表达和/或复制将被阻断。 通过递送剪接切换寡核苷酸来校正引入的缺陷并恢复病毒或载体的生物学功能,包括细胞溶解性质,这些突变的致死作用以受控的方式被还原。