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Generation of biological pacemaker by in vivo genome editing

Research Project

Project/Area Number 18K15882
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53020:Cardiology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Ihara Kensuke  東京医科歯科大学, 難治疾患研究所, 助教 (50770210)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords生物学的ペースメーカ / ゲノム編集 / 徐脈性不整脈
Outline of Final Research Achievements

In the current medical therapy, electrical pacemaker is the only treatment for bradycardia, however, it requires the surgery to implant or exchange which is accompanied by the risk of serious complications. The purpose of this study was to develop the novel technology of noninvasive in situ generation of biological pacemaker utilizing in vivo genome editing. So far, the generated biological pacemaker in this study have not exhibited sufficient pacemaker activity to maintain the murine heart function, and the further study will be required. Finally, we successfully established the novel technique to induce the highly cell type-specific expression of gene of interest by inserting its DNA sequence to the target site on genomic DNA in vivo with intravenous injection, which can be applied to the various organ and cells other than the heart.

Academic Significance and Societal Importance of the Research Achievements

本研究により得られた“静脈注射により目的の遺伝子を生体内の目的の細胞に導入し発現させる技術”は本研究の標的である心臓だけでなく、他臓器にも応用可能な普遍的な技術でありその発展性は大きい。さらに生物学的ペースメーカのような疾患治療などの医療応用だけでなく、様々な生物学的実験に応用が可能であり、今後の基礎研究に寄与する意義のある成果が得られた。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2020 2019 2018

All Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Pannexin-1 Contributes to Maintenance of Cardiac Function against Acute Pressure-overload and Rapid Ventricular Pacing.2020

    • Author(s)
      Ihara K, Sasano T, Kentaro T, Yamazoe M, Furukawa T.
    • Organizer
      The 97th Annual Meeting of the Physiological Society of Japan.
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
  • [Presentation] 光学マッピング法による心不全モデルマウスにおける心房性不整脈の電気生理学的特性評価.2020

    • Author(s)
      岩宮賢, 井原健介, 富井直輝, 山崎正俊, 黒柳秀人, 佐久間一郎, 古川哲史, 笹野哲郎.
    • Organizer
      心電学関連研究会2020.
    • Related Report
      2020 Annual Research Report
  • [Presentation] Intolerance to Rapid Ventricular Pacing and Coronary Hypoplasty in Pannexin-1 Knockout Mouse Heart.2019

    • Author(s)
      Ihara K, Sasano T, Yamazoe M, Furukawa T.
    • Organizer
      The 83rd Annual Scientific Meeting of the Japanese Circulation Society.
    • Related Report
      2019 Research-status Report
  • [Presentation] Local Injection of Charged Hydroxyapatite Nanoparticle Attenuates the Myocardial Injury in Murine Myocardial Infarction Model.2019

    • Author(s)
      Chiba R, Yamazoe M, Ihara K, Komuro H, Nagai A, Furukawa T, Sasano T.
    • Organizer
      The 83rd Annual Scientific Meeting of the Japanese Circulation Society.
    • Related Report
      2018 Research-status Report
  • [Presentation] Intolerance to Rapid Ventricular Pacing in Pannexin-1 Knockout Mouse Heart.2018

    • Author(s)
      Ihara K, Sasano T, Yamazoe M, Furukawa T.
    • Organizer
      The 11th Asia-pacific Heart Rhythm Society Scientific Session. 2018. Oct. Taipei, Taiwan.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pacemaker activity generated by CRISPR/Cas9 based genome editing for Kcnj2.2018

    • Author(s)
      Ihara K, Sasano T, Yamazoe M, Furukawa T.
    • Organizer
      The 2nd JCS Council Forum on Basic CardioVascular Research.
    • Related Report
      2018 Research-status Report
  • [Presentation] Intolerance to Rapid Ventricular Pacing and Coronary Insufficiency in Pannexin-1 Knockout Mouse Heart.2018

    • Author(s)
      Ihara K, Sasano T, Yamazoe M, Furukawa T.
    • Organizer
      第65回日本不整脈心電学会学術大会.
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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