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Mol Cells. 2011 Dec;32(6):543-8. doi: 10.1007/s10059-011-0160-1. Epub 2011 Nov 3.

Selection and optimization of asymmetric siRNA targeting the human c-MET gene.

Author information

1
Global Research Laboratory for RNAi Medicine, Department of Chemistry and Brain Korea 21 School of Chemical Materials Science, Sungkyunkwan University, Suwon 440-746, Korea.

Abstract

The silencing of specific oncogenes via RNA interference (RNAi) holds great promise for the future of cancer therapy. RNAi is commonly carried out using small interfering RNA (siRNA) composed of a 19 bp duplex region with a 2-nucleotide overhang at each 3' end. This classical siRNA structure, however, can trigger non-specific effects, which has hampered the development of specific and safe RNAi therapeutics. Previously, we developed a novel siRNA structure, called asymmetric shorter-duplex siRNA (asiRNA), which did not cause the non-specific effects triggered by conventional siRNA, such as off-target gene silencing mediated by the sense strand. In this study, we first screened potent asiRNA molecules targeting the human c-MET gene, a promising anticancer target. Next, the activity of a selected asiRNA was further optimized by introducing a locked nucleic acid (LNA) to maximize the gene silencing potency. The optimized asiRNA targeted to c-MET may have potential as a specific and safe anticancer RNAi therapeutic.

PMID:
22058018
PMCID:
PMC3887682
DOI:
10.1007/s10059-011-0160-1
[Indexed for MEDLINE]
Free PMC Article

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