2013 Fiscal Year Final Research Report
Medicinal Application of Functional Machinery for non-coding RNAs
| Project Area | Functional machinery for non-coding RNAs |
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| Project/Area Number |
21115008
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Tokyo University of Science (2013)
The University of Tokyo (2009-2012) |
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Principal Investigator |
WADA Takeshi 東京理科大学, 薬学部, 教授 (90240548)
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| Co-Investigator(Kenkyū-buntansha) |
TAKESHITA Fumitaka 独立行政法人国立がん研究センター研究所, 分子細胞治療研究分野, 主任研究員 (40466199)
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| Project Period (FY) |
2009-07-23 – 2014-03-31
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| Keywords | 非コードRNA / 核酸医薬 / ホスホロチオエートRNA / 立体制御 / siRNA / がん |
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| Research Abstract |
A practical method for the synthesis of stereoregulated phaosphorothioate RNA (PSRNA) was established. By using novel nucleoside oxazaphospholidine monomers, various P-stereoregulated PSRNAs including PS-siRNAs were successfully synthesized. Using the resultant PS-RNAs, we demonstrated that the PS-RNA with an all-Rp-phosphorothioate backbone formed a more stable duplex with the complementary RNA than the unmodified counterpart, whereas duplexes consisting of an all-Sp-PS-RNA or a stereo-random counterpart were significantly destabilized. The stability of PS-siRNA was assessed by treatment with RNA degradation enzymes. The siRNA harboring a single PS bond located from center to 3' side of its sequence and the Sp isomer of PS-siRNA showed higher stabilities compared with the Rp isomer. Furthermore, five consecutive PS bonds on the end of 3'-terminal side of siRNAs more contributed the stabilization of themselves and induction of RNAi activity on a mouse model of human breast cancer.
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