Single Administration of AAV-mAtp6v1b2 Gene Therapy Rescues Hearing and Vestibular Disorders Caused by Atp6v1b2-Induced Lysosomal Dysfunction in Hair Cells.

ABSTRACT: Haploinsufficiency of the ATP6V1B2, a subunit of V-ATPases, underlies genetic disorders including Dominant deafness-onychodystrophy (DDOD), deafness, onychodystrophy, osteodystrophy, mental retardation and seizures (DOORS), and Zimmermann-Laband syndromes, all characterized by congenital hearing loss and onychodystrophy. Effective therapies for ATP6V1B2-associated hearing loss remain elusive. The study generates a hair cell-specific knockout mouse (Atp6v1b2^fl/fl;Atoh1^Cre/+) recapitulating the human phenotypes, with pathological features including hair cell loss and abnormal lysosomal morphology and function. To enhance therapeutic precision and minimize toxicity, an optimized adeno-associated virus-inner ear vector incorporating promoter enhancer 3 (AAV-ie-Eh3) is eng

SUBMITTER: Wei G 

PROVIDER: S-EPMC12362768 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature