| Budget Amount *help |
¥124,280,000 (Direct Cost: ¥95,600,000、Indirect Cost: ¥28,680,000)
Fiscal Year 2013: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2012: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2011: ¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000)
Fiscal Year 2010: ¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000)
Fiscal Year 2009: ¥27,820,000 (Direct Cost: ¥21,400,000、Indirect Cost: ¥6,420,000)
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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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