AAV-mediated Gene Therapy for Hereditary Deafness: Progress and Perspectives.

Area of Science:

• Genetics
• Otolaryngology
• Molecular Therapy

Background:

• Hereditary deafness is a common sensory disorder with over 100 identified genes.
• Current treatments are limited to hearing aids and cochlear implants.
• Gene therapy presents a potential therapeutic strategy for genetic hearing loss.

Purpose of the Study:

• To provide a comprehensive review of gene therapy for hereditary deafness.
• To discuss preclinical studies and recent advancements.
• To highlight challenges in adeno-associated virus (AAV)-mediated gene therapy for inner ear disorders.

Main Methods:

• Review of preclinical studies in genetic deafness models.
• Analysis of clinical advancements in gene therapy for hereditary deafness.
• Examination of AAV vector-based gene delivery for inner ear applications.

Main Results:

• Gene therapy has restored hearing in over 20 types of genetic deafness mouse models.
• Successful treatment of hereditary autosomal recessive deafness 9 (DFNB9) due to OTOF mutations demonstrates translational potential.
• AAV-mediated gene therapy shows promise but requires precision for diverse genetic forms and inner ear cell types.

Conclusions:

• Gene therapy is a viable and evolving treatment for hereditary deafness.
• The success in DFNB9 serves as a paradigm for other genetic deafness forms.
• Further research into precision gene therapy is crucial for overcoming challenges related to inner ear complexity and AAV transduction efficiency.