Molecular Properties, Functional Mechanisms, and Applications of Sliced siRNA

Guihua Sun, Spencer Yele Yeh, Christine Wan Yin Yuan, Margaret Jean Yih Chiu, Bryan Shing Hei Yung, Yun Yen

研究成果: 雜誌貢獻文章同行評審

15 引文 斯高帕斯(Scopus)

摘要

Using pre-miR-451 as a model molecule, we have characterized the general molecular properties of small hairpin RNAs that are processed into potent small interfering RNAs (siRNA) by Argonaute2 (Ago2). The Ago2-sliced siRNAs (sli-siRNAs) have the same silencing potency as the classical Dicer diced siRNAs (di-siRNAs) but have dramatically reduced unwanted sense strand activities. We have built vectors with the constitutive or inducible U6 promoter that can express sli-siRNAs in mammalian cells, in which the sli-siRNAs can be correctly processed to repress target genes. As a proof of principle for potential applications of sli-siRNAs in vivo, we show that the expression of one Ago2 shRNA-1148 in HCT-116 colon cancer cells knocked down RRM2 expression and reduced the proliferation and invasiveness of the cells. The defined sli-siRNA model molecules and the expression systems established in this study will facilitate the design and application of sli-siRNAs as novel potent RNAi triggers with reduced off-target effects.

原文英語
文章編號e221
頁(從 - 到)e221
期刊Molecular Therapy - Nucleic Acids
4
發行號1
DOIs
出版狀態已發佈 - 一月 27 2015
對外發佈

ASJC Scopus subject areas

  • 分子醫學
  • 藥物發現

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