The predawn dilemma in adeno-associated virus-based gene therapies for hereditary deafness.

Hearing loss is a prevalent organ-specific disorder affecting individuals throughout their lifespan, with over 466 million cases reported globally. The conditions can be classified into two broad categories: hereditary and nonhereditary. HHL, caused by genetic mutations or chromosomal abnormalities, can be divided into nonsyndromic (NSHL) and syndromic (SHL) subtypes. NSHL presents as isolated auditory impairment without systemic manifestations, whereas SHL involves concurrent dysfunction in other organ systems. Nonhereditary hearing loss typically results from infections, ototoxic drugs, noise exposure, trauma, or age-related degeneration. Current clinical interventions focus on symptom management through hearing aids and cochlear implants, as no curative treatment exists for genetic forms. Recent studies have shown the therapeutic potential of gene therapy in animal models of genetic deafness, although clinical translation faces challenges, including viral vector safety, transfection efficiency, and target specificity. This systematic review synthesizes current progress in gene therapy for HHL and evaluates barriers to clinical implementation, offering insights for future translational studies.