Investigation of mechanisms of action of RNAi related nucleic acid drugs by imaging analyses
| Project/Area Number |
20K05745
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 37030:Chemical biology-related
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| Research Institution | Nagoya University |
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Principal Investigator |
Kamiya Yukiko 名古屋大学, 工学研究科, 准教授 (00527947)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 核酸医薬 / nucleic acid drug / anti-miRNA / miRNA / siRNA / RNAi / RISC / 可視化解析 / アンチセンス核酸 |
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| Outline of Research at the Start |
本研究は、非環状型人工核酸からなるsiRNAおよびAMOの活性発現機構を明らかにすることを目的としている。その一環として、siRNAやAMOの活性複合体を捉えるために、AMO-miRISCおよびsiRISC-mRMA複合体を検出する手法を開発し、細胞内可視化解析を実施する。
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| Outline of Final Research Achievements |
siRNAs and antisense nucleic acids are expected to be nucleic acid drugs that inhibit disease-related RNAs. The purpose of this study was to elucidate the mechanism of activity of siRNA and anti-miRNA nucleic acids designed by acyclic artificial nucleic acids. For this we attempted to developed the scheme to perform intracellular visualization analyses. To detect the expected complexes of these functional nucleic acids with RISC, we designed the methods that enable signal amplification by RCA system or FRET detection only when the complexes are formed. We succeeded in the observation of fluorescent signals from the expected complex in cells. Based on our results, we proposed the mechanism of action of the functional nucleic acids.
This approach is a valuable tool for further understanding of the mechanism of the nucleic acid drugs and contributing to the development of more effective, and safer therapeutic anti-miR drugs.
The result is currently being submitted for publication.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で開発された手法や細胞生物学的知見は、核酸医薬の作用機序の解明に貢献すると期待される。また、得られた知見を活用することで、より効果的で安全なsiRNAや抗miR核酸の開発に貢献すると期待される。
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Report
(4 results)
Research Products
(34 results)
