Investigation of mechanisms of action of RNAi related nucleic acid drugs by imaging analyses

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K05745
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Nagoya University
• Principal Investigator: Kamiya Yukiko 名古屋大学, 工学研究科, 准教授 (00527947)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 核酸医薬 / nucleic acid drug / anti-miRNA / miRNA / siRNA / RNAi

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.

Free Research Field

生体関連化学

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。