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Intracellular stability of 2'-OMe-4'-thioribonucleoside modified siRNA leads to long-term RNAi effect
| 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 |
| URI: | http://hdl.handle.net/2115/49693 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 彰
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