| Project/Area Number |
16K18911
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Gifu University |
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Principal Investigator |
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| Research Collaborator |
KITADE YUKIO 愛知工業大学, 工学部, 教授 (20137061)
IKEDA MASATO 岐阜大学, 工学部, 教授 (20432867)
AYA SHIBATA 岐阜大学, 工学部, 助教 (50462693)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 核酸医薬 / 機能性短鎖RNA / 環境応答 / 分解酵素耐性 / 簡便合成 / CuAAC / ポスト修飾 / 効率的合成 / 薬学 / 有機化学 / 生理活性 |
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| Outline of Final Research Achievements |
Small interfering RNAs (siRNAs) and microRNAs inhibit gene expression by RNA interference (RNAi) and thus have great potential as nucleic acid-based drugs. However, naked RNA strands have many problems that hinder their application as therapeutics, such as their rapid degradation in biological fluids, poor cellular uptake, and off-target effects. In the course of our study, we focused on studying siRNAs containing nucleoside mimics in their 3'-termini. In this study, we found that furanoid glycals could be useful as stimulus-responsive units. In addition, it was found that introduction of 2-O-benzylated abasic nucleoside (RHOBn) at the 3'-end of an siRNA greatly improves resistance towards various nucleases. Furthermore, we have developed a scalable synthetic method for phosphoramidite derivatives of artificial nucleosides including 1-deoxy-1-ethynyl-β-D-ribofuranose (RE). These results should help to advance the development of RNAi-based medicine.
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