Development of gene therapy for GJB2 related hearing loss targeting the mature mouse inner ear

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K09387
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Juntendo University
• Principal Investigator: Iizuka Takashi 順天堂大学, 医学部, 非常勤助教 (40372932)
• Co-Investigator(Kenkyū-buntansha): 神谷 和作 順天堂大学, 医学部, 准教授 (10374159)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: GJB2 / 遺伝性難聴

Outline of Final Research Achievements

In this study, we developed a new AAV vector with improved amino acids in the capsid　region for inner ear gene therapy, and attempted to develop a surgical technique for administering this AAV vector to the endolymph in mature mice. As a result of examining　the administration method, a fused silica tube with an　inner diameter of 0.075 mm was　inserted from the posterior semicircular canal to the vestibular direction, and 10-12 μl of the　virus solution was perfused at a flow rate of 60-90 μl/h to perfuse the inner ear endolymph　efficiently. It was possible to reach the tissue, especially the cochlear supporting cells. By　the same method, CX26 gene was introduced into cochlear supporting cells with high　efficiency, and we succeeded in significantly　restoring the hearing of mature CX26-deficient　mice.

Free Research Field

遺伝性難聴

Academic Significance and Societal Importance of the Research Achievements

遺伝性難聴は1600出生に一人と高頻度に発生するが、その根本的治療法はなく次世代の治療法開発が期待されている。本研究ではAAVベクター投与法を改良し、ヒト臨床応用への対象として現実的である成熟マウスでの聴力回復を実現させる新たな遺伝子導入法のが開発された。これにより遺伝子改変マウスを用いた内耳遺伝子治療の非臨床PoCの取得が可能となり、遺伝性難聴への遺伝子治療法を現実的な治療へと近づける学術的及び社会的意義のある研究成果が得られた。