申请人:PROTIVA BIOTHERAPEUTICS, INC.
公开号:US20160115483A1
公开(公告)日:2016-04-28
The present invention provides compositions comprising interfering RNA (e.g., siRNA, aiRNA, miRNA) that target polo-like kinase 1 (PLK-1) expression and methods of using such compositions to silence PLK-1 expression. More particularly, the present invention provides unmodified and chemically modified interfering RNA molecules which silence PLK-1 expression and methods of use thereof. The present invention also provides serum-stable nucleic acid-lipid particles (e.g., SNALP) comprising an interfering RNA molecule described herein, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugated lipid that inhibits aggregation of particles. The present invention further provides methods of silencing PLK-1 gene expression by administering an interfering RNA molecule described herein to a mammalian subject. The present invention additionally provides methods of identifying and/or modifying PLK-1 interfering RNA having immunostimulatory properties. Methods for sensitizing a cell such as a cancer cell to the effects of a chemotherapy drug comprising sequentially delivering PLK-1 interfering RNA followed by the chemotherapy drug are also provided.
本发明提供了包含干扰RNA(例如siRNA、aiRNA、miRNA)的组合物,其靶向波洛样激酶1(PLK-1)表达,并提供了使用这种组合物来沉默PLK-1表达的方法。更具体地说,本发明提供了未修饰和化学修饰的干扰RNA分子,这些分子可以沉默PLK-1表达,并提供了它们的使用方法。本发明还提供了含有干扰RNA分子、阳离子脂质和非阳离子脂质的血清稳定核酸-脂质颗粒(例如SNALP),这些颗粒还可以进一步包含抑制颗粒聚集的共轭脂质。本发明还提供了通过向哺乳动物主体施用本文描述的干扰RNA分子来沉默PLK-1基因表达的方法。本发明还提供了识别和/或修改具有免疫刺激性能的PLK-1干扰RNA的方法。此外,还提供了一种通过顺序输送PLK-1干扰RNA后接着化疗药物来使细胞(如癌细胞)对化疗药物产生敏感性的方法。