Development of inner ear AAV genome editing therapy for hereditary hearing loss using patient iPS cells and animal models

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03089
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Juntendo University
• Principal Investigator: Ikeda Katsuhisa 順天堂大学, 医学部, 特任教授 (70159614)
• Co-Investigator(Kenkyū-buntansha): 美野輪 治 順天堂大学, 医学部, 非常勤講師 (00181967) ; 神谷 和作 順天堂大学, 医学部, 准教授 (10374159)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 遺伝性難聴 / GJB2変異型難聴モデル / ゲノム編集 / 内耳AAVゲノム / ips由来疾患モデル細胞

Outline of Final Research Achievements

In this study, we have developed a fundamental treatment for hereditary hearing loss using iPS cells and genome editing technology to repair cochlear gap junctions and inner ear cell therapy We established and induced differentiation of iPS cells from a Japanese patient with a typical GJB2 mutation, and obtained disease model cells. Furthermore, we developed a genome-edited knock-in mouse with a typical GJB2 mutation. We also developed a highly efficient vector specialized for GJB2 related hearing loss, and developed a capsid-modified AAV vector for inner ear cells capable of gene transfer to the entire cochlear epithelium and a specific multiple promoter, and filed a patent application (JP-Application 2021-198101). The vector was confirmed to be useful for genome editing to iPS derived cells.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は遺伝性難聴の分子病態・機序を解明する突破口を切り開き、根本的治療の現実化に正面から取り組むもので、画期的な技術を駆使している。これらの画期的な企画はこれまで全く創造されていない極めて独創性の高い研究である。この技術が臨床に適用されると、聴覚医学に新しい局面を迎えることができる。難聴に悩み、苦しむ数百万人の患者への大きな福音となり、国民生活の質的向上をもたらす極めて有意義な研究である。