Gene-Based Strategies for Cochlear Repair and Hearing Restoration: From Molecular Targets to Clinical Translation
DOI:
https://doi.org/10.64784/088Keywords:
cochlear regeneration, gene therapy, sensorineural hearing loss, hair cell regeneration, inner ear gene delivery, translational otology, auditory restorationAbstract
Sensorineural hearing loss remains a major global health challenge due to the limited regenerative capacity of the mammalian cochlea and the predominantly compensatory nature of current therapeutic options. In recent years, gene therapy has emerged as a promising strategy aimed at restoring auditory function by directly targeting the molecular and cellular mechanisms underlying cochlear dysfunction. This review analyzes and synthesizes contemporary advances in cochlear regeneration through gene-based interventions, including gene replacement, gene editing, transcription factor–mediated reprogramming, and RNA-based therapies. The evidence highlights that gene replacement approaches, particularly for monogenic forms of hearing loss with preserved cochlear architecture, currently demonstrate the most direct translational potential. Regenerative strategies focused on reactivating developmental pathways show encouraging structural and functional outcomes, although their long-term integration and stability remain critical challenges. Across all modalities, delivery platforms and administration routes emerge as decisive factors influencing efficacy, safety, and clinical feasibility. Functional auditory outcomes and translational readiness are increasingly emphasized as essential benchmarks for therapeutic relevance. This review also underscores the importance of international collaboration and the inclusion of research and healthcare contexts from Mexico, Colombia, and Ecuador to support equitable translation and implementation. Collectively, the findings position cochlear gene therapy as a rapidly evolving and clinically relevant field, with realistic prospects for biological hearing restoration contingent upon continued interdisciplinary and global efforts.
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