Principles of gene therapy of the inner ear

• Published in: Current opinion in otolaryngology & head and neck surgery
• Main Authors: Lin, Joshua S, Shibata, Seiji B
• Format: Journal Article
• Language: English
• Published: United States 31.07.2025
• Subjects: gene therapy; regenerative therapeutics; stem cell transplant; cellular reprogramming; hearing rehabilitation
• ISSN: 1531-6998
• DOI: 10.1097/MOO.0000000000001067

Preclinical auditory research uncovers mechanisms underlying hearing loss and reveals novel therapeutic targets. Inner ear gene therapy offers an attractive alternative to current treatments for deafness. An in-depth understanding of the principles of gene therapy is essential to the design of cochlear gene therapy studies, which must be meticulously selected based on the etiology, pathophysiology, and mechanisms of hearing loss. The purpose of our article is to provide an updated and succinct review of cochlear gene therapy. Advances in molecular technology have enabled numerous proof-of-principle studies in recent years, testing the feasibility of protective, restorative, and regenerative cochlear gene therapy. Recent findings have demonstrated how the delivery of neurotrophic factor transgenes can potentially improve hearing in hidden hearing loss. Restorative gene therapy, carrying the OTOF gene, has restored hearing in human subjects in clinical trials. Additionally, ongoing efforts are underway to regenerate sensory cells in the cochlea using cocktails of transcription factors in postdeafened animal models. Recent successes in clinical trials for cochlear gene therapy are encouraging; however, preclinical auditory research remains a high priority and necessity. Future advancements in basic science research may enable the prevention or cure of deafness through cochlear gene therapy.