Emerging gene and stem cell therapies for hereditary hearing loss: from molecular correction to regenerative reconstruction

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Abstract

Hearing loss is among the most common sensory impairments globally and remains a significant unmet clinical challenge. Current rehabilitative approaches, such as hearing aids and cochlear implants, provide partial functional compensation but fail to restore the structural and physiological integrity of the cochlea. This review summarizes progress in therapeutic development targeting key deafness-associated genes, including OTOF, GJB2, and SLC26A4, highlighting the rationale, current clinical evidence, and major translational challenges. We further discuss the potential of combining gene therapy with stem cell-based approaches to promote inner ear regeneration and restore sensorineural function. Emerging technologies such as CRISPR/Cas, adeno-associated virus, and induced pluripotent stem cell-derived otic progenitors have opened new avenues for causal correction and tissue reconstruction. Integrated therapeutic models that combine gene or stem cell therapy with cochlear implants are reshaping the treatment paradigm from symptom management to biological repair. Advances in gene editing, gene delivery, and stem cell technologies are establishing these approaches as promising treatments for hereditary hearing loss, with ongoing progress expected to accelerate clinical translation despite remaining challenges in delivery efficiency, immune responses, ethics, and long-term efficacy. Collectively, these advances mark a pivotal step toward personalized and regenerative interventions for hereditary hearing loss.

Keywords

hereditary hearing loss / gene therapy / cochlear implant / stem cell therapy / CRISPR/Cas / adeno-associated virus (AAV) / regeneration

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