Development of a highly functional artificial mRNA platform for the realization of mRNA medicine

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K12644
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Kyoto University
• Principal Investigator: Ohno Hirohisa 京都大学, iPS細胞研究所, 特定拠点助教 (90612391)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: mRNA / 遺伝子治療 / キャップ

Outline of Final Research Achievements

In recent years, gene introduction methods utilizing synthetic messenger RNA (mRNA), as exemplified by RNA vaccines, have garnered significant attention. RNA is considered highly safe due to its lower risk of causing unexpected mutations in genomic DNA; however, it also faces challenges such as instability. This study aims to address these challenges and develop more practical synthetic mRNA. To improve mRNA stability and protein expression levels, I focused on the 5’ cap structure, establishing methods to introduce various modifications at the cap site and identifying modified caps that enhance protein expression levels. Additionally, I worked on developing mRNA capable of expressing proteins exclusively in target cells.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、mRNAの5’キャップ構造に多様な化学修飾を導入できる方法を確立した。本研究で見出したタンパク質発現レベルを向上させる修飾キャップは人工mRNAの作製に利用できる。また、修飾キャップの化学構造を利用することで、キャップ部位を蛍光色素などの様々な機能性分子で標識できることを示した。これはRNA研究のための新たなツールになりうる。さらに、標的細胞のみでタンパク質発現を行えるmRNAの開発を行った。これは副作用の低減につながり、より安全なmRNA医薬の実現の役立つと考えられる。