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2019 Fiscal Year Final Research Report

Elucidation of global metabolic control mechanisms by microRNA-33a/b and development of specific regulatory strategy using artificial nucleic acid

Research Project

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Project/Area Number 17H04177
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cardiovascular medicine
Research InstitutionKyoto University

Principal Investigator

Ono Koh  京都大学, 医学研究科, 准教授 (00359275)

Co-Investigator(Kenkyū-buntansha) 堀江 貴裕  京都大学, 医学研究科, 助教 (20565577)
Project Period (FY) 2017-04-01 – 2020-03-31
KeywordsマイクロRNA / iPS細胞 / 核酸医薬
Outline of Final Research Achievements

We revealed that microRNA(miR)-33a/b have essential roles in low HDL-C, atherosclerosis, aortic aneurysm, fibrosis, non-alcoholic steatohepatitis, hypertension, Alzheimer disease, and activation of sympathetic nerve by the use of genetically modified induced pluripotent stem cell and mice. In these experiments, it was shown that miR-33a/b have different target genes in each cell or tissue. Moreover, we developed anti-miR-33a/b oligonucleotides that can selectively suppress the levels of miR-33a or -33b. We applied these oligonucleotides to several disease models and filed a patent for the treatment of aortic aneurysm. We are going to conduct clinical research to identify the clinical application of these oligonucleotides.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、microRNA-33a/bが低HDL-C、動脈硬化症、動脈瘤、線維化、NASHを含む慢性炎症、高血圧症、アルツハイマー症、交感神経系の活性化に共通する発症基盤であることが明らかになった。これは我々の作成した遺伝子改変マウスによってのみ明らかにすることができた点であり、学術的意義が高いと考えられる。さらに、miR-33aおよび33bを個別に制御できる架橋型人工核酸を開発し、複数の疾患モデルにおいて治療効果の検討を行っている。すでに大動脈瘤については治療法の特許申請中であり、今後さらに治療可能な疾患が増えることが予想されるため、臨床的・社会的意義も高いと考えられる。

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Published: 2021-02-19   Modified: 2025-01-30  

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