Link to Pubmed [PMID] – 40263131
Link to DOI – 10.1007/s00335-025-10126-y
Mamm Genome 2025 Jun; 36(2): 417-443
Gene therapy offers significant promise for treating inner ear disorders, but its clinical translation requires robust preclinical validation, often reliant on animal models. This review examines the role of these models in advancing gene therapeutics for inherited inner ear disorders, focusing on successes, challenges, and treatment solutions. By providing a precise understanding of disease mechanisms, these models offer a versatile preclinical platform that is essential for assessing and validating therapies. Successful gene supplementation and editing have shown potential in restoring hearing and balance functions and preventing their decline. However, challenges such as limitations in gene delivery methods, surgical access, immune responses, and discrepancies in disease manifestation between animal models and humans hinder clinical translation. Current efforts are dedicated to developing innovative strategies aimed at enhancing the efficiency of gene delivery, overcoming physical barriers such as the blood-labyrinth barrier, improving target specificity, and maximizing therapeutic efficacy while minimizing adverse immune responses. Diverse gene supplementation and editing strategies, along with evolving technologies, hold promise for maximizing therapeutic outcomes using disease relevant models. The future of inner ear gene therapeutics will hinge on personalized therapies and team science fueling interdisciplinary collaborations among researchers, clinicians, companies, and regulatory agencies to expedite the translation from bench to bedside and unlock the immense potential of precision medicine in the inner ear.