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Silencing method of Polo-like kinase expression using RNA interference

机译:RNA干扰沉默Polo样激酶表达的方法

摘要

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.
机译:本发明提供了包含靶向polo样激酶1(PLK-1)表达的干扰RNA(例如,siRNA,aiRNA,miRNA)的组合物,以及使用这种组合物沉默PLK-1表达的方法。更具体地,本发明提供了使PLK-1表达沉默的未修饰的和化学修饰的干扰RNA分子及其使用方法。本发明还提供了血清稳定的核酸脂质颗粒(例如,SNALP),其包含本文所述的干扰RNA分子,阳离子脂质和非阳离子脂质,其可以进一步包含抑制颗粒聚集的缀合脂质。本发明进一步提供了通过向哺乳动物受试者施用本文所述的干扰RNA分子来沉默PLK-1基因表达的方法。本发明另外提供了鉴定和/或修饰具有免疫刺激特性的PLK-1干扰RNA的方法。还提供了使细胞(例如癌细胞)对化疗药物的作用敏感的方法,该方法包括先递送PLK-1干扰RNA,然后再放化疗药物。

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