Dawn of auditory restoration: meta-review of genetic therapy advances for congenital hearing loss

Congenital hearing loss (CHL), affecting 1-3 per 1000 newborns globally, represents a paradigm shift in therapeutic development with the advent of genetic interventions. This meta-review synthesizes evidence from 42 clinical and preclinical studies (2020-2025) demonstrating that adeno-associated virus (AAV)-mediated gene therapy has successfully restored auditory function in patients with autosomal recessive deafness 9 (DFNB9), with mean auditory brainstem response (ABR) thresholds improving from 106±9 dB to 52±30 dB within one-month post-intervention. Younger patients (5-8 years) exhibited near-complete recovery, while adults showed clinically significant improvements. The emergence of novel delivery vectors (including engineered AAVs and lipid nanoparticles), CRISPR-based editing strategies, and innovative cellular entry pathways (AAVR2 receptor) has expanded the therapeutic landscape. Despite challenges in vector tropism, immune responses, and accessibility, genetic therapies are poised to transform CHL management from amplification to biological restoration. Future research must prioritize solutions for dominant genetic forms, optimal intervention timing, and cortical reintegration pathways.