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Mammalian biocomputing platform by translational modulators

Research Project

Project/Area Number 19K16110
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 43060:System genome science-related
Research InstitutionKyoto University

Principal Investigator

Kawasaki Shunsuke  京都大学, iPS細胞研究所, 特定研究員 (10816036)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords人工遺伝子回路 / 翻訳制御 / RNA/RNP / 細胞コンピューティング / 合成生物学
Outline of Research at the Start

大規模な人工遺伝子回路は、細胞機能を自在に制御できるため、合成生物学及び医療研究において注目されつつある。中でも安全性、設計の容易さ、応用可能性の豊富さを兼ね備えている「翻訳を制御できる遺伝子回路の構築」が望まれている。本研究では、翻訳制御に必要な人工分子デバイスの種類を拡充し、大規模な翻訳制御回路の構築原理を解明する。このような遺伝子回路によって、将来的には治療機能を持つ細胞の挙動や、遺伝子治療薬の機能を正確にプログラム可能となる。

Outline of Final Research Achievements

Precise control of gene expression in mammalian cells by using synthetic gene circuits is important for cell engineering and medical applications. In particular, the circuits based on translational modulators can function with various vectors such as synthetic RNAs and replicons which are regarded as the low genomic harm. However, the variety of translational modulators that can be implemented in complex circuits has been limited yet.
We expanded the library of the available translational modulators and also demonstrated that Cas proteins can be repurposed as translational modulators. We designed over 50 different modulators and built over 60 synthetic circuits. These translational modulators have the potential to provide "biological Integrated-Circuits" which facilitate the development of biocomputers.

Academic Significance and Societal Importance of the Research Achievements

本研究では、翻訳制御因子の種類を拡充し、それら翻訳制御因子からなる回路の構成およびその連結様式を検証し、大規模な翻訳制御回路の構築原理の解明を目指した。このような遺伝子回路によって、将来的には治療機能を持つ細胞の挙動や、遺伝子治療薬の機能を正確にプログラム可能となる。これにより、治療効果の強度や、発揮のタイミング、パターンを調節可能な新しい治療戦略を提供できる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (9 results)

All 2021 2020 2019 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (3 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] RNA and protein-based nanodevices for mammalian post-transcriptional circuits2020

    • Author(s)
      Kawasaki Shunsuke、Ono Hiroki、Hirosawa Moe、Saito Hirohide
    • Journal Title

      Current Opinion in Biotechnology

      Volume: 63 Pages: 99-110

    • DOI

      10.1016/j.copbio.2019.11.019

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Orthogonal Protein-Responsive mRNA Switches for Mammalian Synthetic Biology2019

    • Author(s)
      Ono Hiroki、Kawasaki Shunsuke、Saito Hirohide
    • Journal Title

      ACS Synthetic Biology

      Volume: 9 Issue: 1 Pages: 169-174

    • DOI

      10.1021/acssynbio.9b00343

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 哺乳類細胞内で機能するRNAを用いた新規分子検出プラットフォーム2021

    • Author(s)
      川﨑俊輔、桑原傑、齊藤博英
    • Organizer
      MBSJ分子生物学会 (2021年会)
    • Related Report
      2021 Annual Research Report
  • [Presentation] 新規タンパク質応答型mRNAスイッチによる人工遺伝子回路の生細胞内計算能力の拡張2019

    • Author(s)
      川﨑俊輔、小野紘貴、弘澤萌、齊藤博英
    • Organizer
      第12回「細胞を創る」研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 翻訳制御に基づく哺乳類細胞コンピュータ2019

    • Author(s)
      川﨑俊輔、小野紘貴、弘澤萌、齊藤博英
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Remarks] タンパク質を検出する合成mRNAスイッチの拡張:より複雑な細胞操作に向けて

    • URL

      https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/191217-100000.html

    • Related Report
      2019 Research-status Report
  • [Remarks] Four RNA good, 5 RNA better

    • URL

      https://www.cira.kyoto-u.ac.jp/e/pressrelease/news/191217-100000.html

    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] RNA分子2021

    • Inventor(s)
      齊藤博英、川﨑俊輔、桑原傑
    • Industrial Property Rights Holder
      齊藤博英、川﨑俊輔、桑原傑
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-194197
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] mRNAスイッチ及びこれを用いたタンパク質の発現制御方法2019

    • Inventor(s)
      齊藤 博英、川﨑 俊輔、弘澤 萌、小野 紘貴
    • Industrial Property Rights Holder
      齊藤 博英、川﨑 俊輔、弘澤 萌、小野 紘貴
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-218386
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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