Optical regulation system of mRNA translation with spatiotemporal and cell-type specificity

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K20696
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Nakanishi Hideyuki 東京医科歯科大学, 生体材料工学研究所, 助教 (90722885)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: mRNA医薬 / 遺伝子治療 / 合成生物学 / 翻訳 / 遺伝子発現制御

Outline of Final Research Achievements

mRNA drugs can make cells to express any therapeutic transgenes, but they may induce adverse effects due to off-target or excessive expression. Therefore, in this study, we developed light and protein-responsive systems that control the translation from mRNAs to proteins. These translational control systems enable selective expression in cells which are irradiated by light or expressing a specific target protein.
Furthermore, we also developed the system to post-translationally control the therapeutic protein function. In this system, the proteins are translated from mRNA as inactive forms, and activated only under specific conditions.
These systems will help the development of mRNA drugs with high therapeutic effects and low adverse effects.

Free Research Field

遺伝子治療

Academic Significance and Societal Importance of the Research Achievements

翻訳段階ならびに翻訳後段階でmRNA医薬を制御し標的細胞選択的な治療遺伝子発現を可能にした本研究成果は、正常細胞への影響を抑えつつがん細胞を死滅させるといったような、高い治療効果と低い副作用を兼ね備えたmRNA医薬の実現に貢献するものと考えられる。
また、mRNA医薬を直接投与する以外にも、再生医療・細胞治療の準備段階において移植したい細胞種だけ残して副作用の原因となる細胞種は死滅させるといった利用法も考えられる。同様に、ドラッグスクリーニング等の研究に用いる細胞種を様々な細胞種が混在した集団から選別といった応用も可能である。
以上のように、本研究成果は様々な治療法の発展への寄与が期待できる。