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Sun G, Yeh SY, Yuan CW, et al. Molecular Properties, Functional Mechanisms, and Applications of Sliced siRNA. Mol Ther Nucleic Acids. 2015;4:e221doi: 10.1038/mtna.2014.73.
Sun, G., Yeh, S. Y., Yuan, C. W., Chiu, M. J., Yung, B. S., & Yen, Y. (2015). Molecular Properties, Functional Mechanisms, and Applications of Sliced siRNA. Molecular therapy. Nucleic acids, 4e221. https://doi.org/10.1038/mtna.2014.73
Sun, Guihua, et al. "Molecular Properties, Functional Mechanisms, and Applications of Sliced siRNA." Molecular therapy. Nucleic acids vol. 4 (2015): e221. doi: https://doi.org/10.1038/mtna.2014.73
Sun G, Yeh SY, Yuan CW, Chiu MJ, Yung BS, Yen Y. Molecular Properties, Functional Mechanisms, and Applications of Sliced siRNA. Mol Ther Nucleic Acids. 2015 Jan 20;4:e221. doi: 10.1038/mtna.2014.73. PMID: 25602583; PMCID: PMC4345305.
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Mol Ther Nucleic Acids. 2015 Jan 20;4:e221. doi: 10.1038/mtna.2014.73.

Molecular Properties, Functional Mechanisms, and Applications of Sliced siRNA.

Molecular therapy. Nucleic acids

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

Affiliations

  1. Department of Molecular Pharmacology, Beckman Research Institute of the City of Hope, Duarte, California, USA.
  2. Summer Interns, Beckman Research Institute of the City of Hope, Duarte, California, USA.

PMID: 25602583 PMCID: PMC4345305 DOI: 10.1038/mtna.2014.73

Abstract

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.

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