Development of high-precision genome editing technology to prevent Alzheimer's disease through disease-protective editing.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20893
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Hino Tomohiro 京都府立医科大学, 医学部附属病院, 専攻医 (50967578)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: アルツハイマー病 / ゲノム編集 / deep mutational scanning

Outline of Final Research Achievements

We performed a comprehensive analysis on single nucleotide polymorphisms in Alzheimer's disease and successfully identified a disease-protective polymorphism with reduced Aβ levels. In addition, we confirmed that Aβ was reduced in a mouse model of Alzheimer's disease in which the protective polymorphism was knocked in. Furthermore, we were able to confirm acquired genome editing by intracranial local injection of adeno-associated virus carrying an adenine-based editor. Pathological evaluation and behavioural experiments will continue to confirm the therapeutic effect.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

高齢化社会に伴う認知症患者数の増加は社会的な問題であり、その約3分の2を占めるアルツハイマー病の患者は今後増加していくことが予想される。本研究ではアルツハイマー病に対して発症予防効果がある一塩基多型を同定することに成功し、その予防効果を細胞実験およびアルツハイマーモデルマウスで示すことができため、今後の認知症研究において大きな一歩となると考えれられる。