Advances and challenges in adeno-associated viral inner-ear gene therapy for sensorineural hearing loss

• Published in: Molecular therapy. Methods & clinical development 2021-06, Vol.21, p.209-236
• Main Authors: Bankoti, Kamakshi, Generotti, Charles, Hwa, Tiffany, Wang, Lili, O’Malley, Bert W., Li, Daqing
• Format: Article
• Language: English
• Subjects: AAV; inner ear; Review; sensorineural hearing loss
• ISSN: 2329-0501; 2329-0501
• DOI: 10.1016/j.omtm.2021.03.005

There is growing attention and effort focused on treating the root cause of sensorineural hearing loss rather than managing associated secondary characteristic features. With recent substantial advances in understanding sensorineural hearing-loss mechanisms, gene delivery has emerged as a promising strategy for the biological treatment of hearing loss associated with genetic dysfunction. There are several successful and promising proof-of-principle examples of transgene deliveries in animal models; however, there remains substantial further progress to be made in these avenues before realizing their clinical application in humans. Herein, we review different aspects of development, ongoing preclinical studies, and challenges to the clinical transition of transgene delivery of the inner ear toward the restoration of lost auditory and vestibular function. [Display omitted] With recent substantial advances in understanding the mechanisms of sensorineural hearing loss (SNHL), gene therapy has emerged as a promising strategy for its treatment. There are several promising examples of gene therapy in animal models with SNHL; however, substantial advancements need to be made prior to their clinical application.