Generation of biological pacemaker by in vivo genome editing

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15882
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Tokyo 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
• Keywords: 生物学的ペースメーカ / ゲノム編集

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.

Free Research Field

循環器内科学

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。