[Advances in research on the molecular mechanisms and gene therapy of hereditary hearing impairment].

Hereditary hearing impairment represents a significant etiology of language and social dysfunction in both children and adults, primarily caused by genetic factors. To date, over 150 genes have been identified in association with this disorder. The pathogenic mechanisms involve multiple molecular levels, including abnormalities in hair cell cytoskeleton and stereociliary structure, dysfunction of intercellular gap junctions (e.g., GJB2, GJB6), dysregulation of ion channels and transporters (e.g., SLC26A4, KCNQ4), alterations in extracellular matrix composition, and disruption of intracellular signaling pathways. In recent years, research has expanded to investigate the role of the inner ear immune microenvironment in this condition, with emerging evidence suggesting that immune dysregulation may contribute to disease initiation and progression. Therapeutically, novel strategies such as adeno-associated virus (AAV)-based gene replacement therapy, CRISPR/Cas-mediated gene editing systems, and lipid nanoparticle (LNP)-delivered mRNA therapeutics have demonstrated partial restoration of auditory function in animal models of hereditary hearing impairment involving genes such as TMC1, OTOF, and GJB2, with some approaches having advanced to clinical trial stages. This article systematically summarizes recent advances in the molecular mechanisms, immune microenvironment involvement, and gene therapy strategies for hereditary hearing impairment, delineates the research trajectory from gene discovery and mechanistic elucidation to therapeutic development, and discusses future translational research directions and clinical challenges.