Tropism of AAV vectors in adult mammalian inner ear subtypes

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18727
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Shinshu University
• Principal Investigator: Yoshimura Hidekane 信州大学, 学術研究院医学系(医学部附属病院), 講師 (10612997)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 遺伝性難聴 / 遺伝子治療 / アデノ随伴ウイルスベクター

Outline of Final Research Achievements

Gene delivery is a key component for the treatment of genetic hearing loss. To date, a myriad of adeno-associated virus (AAV) serotypes and surgical approaches have been employed to deliver transgenes to cochlear hair cells. Herein, we investigated cellular tropism of single injections of AAV serotype 1 (AAV1), AAV2, AAV8, AAV9. We used
the combined round window membrane and canal fenestration (RWM+CF) injection technique for vector delivery. Single AAV2 injections were most robust and transduced
96.7% ± 1.1% of inner hair cells (IHCs) and 83.9% ± 2.0% of outer hair cells (OHCs) throughout the cochlea without causing hearing impairment or hair cell loss.RWM+CF-injected AAV2 provides the highest auditory hair cell transduction efficiency of the AAV serotypes we studied. These findings broaden the application of cochlear gene therapy targeting hair cells.

Free Research Field

難聴、内耳研究

Academic Significance and Societal Importance of the Research Achievements

我々の研究により遺伝性難聴の原因の2/3以上を占めるとされる有毛細胞へ効率的に遺伝子導入を実現できるセロタイプが特定され、遺伝子治療研究において非常に有意義な結果であったと考えられた。