Novel targeting system of circulating non-coding RNAs for the inhibition of cancer metastasis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02087
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 37010:Bio-related chemistry
• Research Institution: Nagasaki University
• Principal Investigator: YAMAYOSHI Asako 長崎大学, 医歯薬学総合研究科(薬学系), 教授 (70380532)
• Co-Investigator(Kenkyū-buntansha): 芦原 英司 京都薬科大学, 薬学部, 教授 (70275197)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: エクソソーム / microRNA / 核酸医薬 / 抗体結合型核酸

Outline of Final Research Achievements

MicroRNAs in exosomes (exosomal miRNAs) are considered as significant targets for cancer therapy. AntimiR oligonucleotides are often used for the functional inhibition of miRNA; however, there are no studies regarding the regulation of exosomal miRNA functions. In this study, we attempted to develop a novel drug delivery system using anti-exosome antibody-antimiR oligonucleotide complexes (ExomiR-Tracker) to hijack exosomes to carry AntimiR oligonucleotides inside exosome-recipient cells. We found that ExomiR-Tracker bound to the exosomes, and then, the complexes were introduced into the recipient cells. We also found that Anti-miR oligonucleotides introduced into the recipient cells can exhibit inhibitory effects on exosomal-miRNA functions in vitro and in vivo. We believe that our strategy would be a promising one for targeting exosomal-miRNAs.

Free Research Field

生体機能関連化学、核酸化学

Academic Significance and Societal Importance of the Research Achievements

我々は、極微量で高度な機能を発揮し、生体制御系に大きな役割を果たしているexosomal-miRNAを標的とした機能性分子の開発に成功した。近年、エクソソームを回収した後、様々な分子を内包させることでDDSとして利用する研究が盛んに行われているが、 我々の開発した手法はエクソソームを単離・精製する必要がなく、体内に直接投与できるという点において一線を画すものである。このExomiR-Trackerは、anti-miR核酸だけでなく、mRNAを標的としたアンチセンス核酸、siRNA、アプタマー、さらには核酸だけでなく低分子化合物を搭載することも可能である。