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Intracellular stability of 2'-OMe-4'-thioribonucleoside modified siRNA leads to long-term RNAi effect

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Title: Intracellular stability of 2'-OMe-4'-thioribonucleoside modified siRNA leads to long-term RNAi effect
Authors: Takahashi, Mayumi Browse this author
Nagai, Chisato Browse this author
Hatakeyama, Hiroto Browse this author →KAKEN DB
Minakawa, Noriaki Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Matsuda, Akira Browse this author →KAKEN DB
Issue Date: Jul-2012
Publisher: Oxford University Press
Journal Title: Nucleic Acids Research
Volume: 40
Issue: 12
Start Page: 5787
End Page: 5793
Publisher DOI: 10.1093/nar/gks204
Abstract: Chemically modified siRNAs are expected to have resistance toward nuclease degradation and good thermal stability in duplex formation for in vivo applications. We have recently found that 2'-OMe-4'-thioRNA, a hybrid chemical modification based on 2'-OMeRNA and 4'-thioRNA, has high hybridization affinity for complementary RNA and significant resistance toward degradation in human plasma. These results prompted us to develop chemically modified siRNAs using 2'-OMe-4'-thioribonucleosides for therapeutic application. Effective modification patterns were screened with a luciferase reporter assay. The best modification pattern of siRNA, which conferred duration of the genesilencing effect without loss of RNAi activity, was identified. Quantification of the remaining siRNA in HeLa-luc cells using a Heat-in-Triton (HIT) qRT-PCR revealed that the intracellular stability of the siRNA modified with 2'-OMe-4'-thioribonucleosides contributed significantly to the duration of its RNAi activity.
Type: article
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 松田 彰

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