The Journal of clinical investigationOct 15, 2025

Gene Editing Therapy Restores Hearing in Mice with Genetic Deafness

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Abstract

This study explores a new gene editing treatment that could help restore hearing in mice suffering from a genetic condition called DFNA41. Using a virus to deliver a gene-editing tool, researchers were able to correct a specific mutation in the inner ear, leading to improved hearing and balance. The treatment not only fixed the hearing loss but also protected the mice from damage caused by loud noises. The findings suggest that early treatment could be even more effective, and the study paves the way for potential therapies for humans with similar genetic hearing loss.

Simplified

Genome editing has the potential to treat genetic hearing loss. However, current editing therapies for genetic hearing loss have shown efficacy only in hearing rescue. In this study, we evaluated a rescue strategy using adeno-associated virus (AAV) type 2-mediated delivery of Staphylococcus aureus Cas9-sgRNA in the mature inner ear of the P2rx2V61L/+ mouse model of autosomal dominant deafness-41 (DFNA41), a dominant, delayed-onset, and progressive hearing loss in humans. We demonstrate that local injection in adult mice results in efficient and specific editing that abolishes the mutation without notable off-target effects or AAV genome integration. Editing effectively restores long-term auditory and vestibular function. Editing further protects P2rx2V61L/+ mice from hypersensitivity to noise-induced hearing loss, a phenotype also observed in patients with DFNA41. Intervention in mice at a juvenile stage broadens the frequency range rescued, highlighting the importance of early intervention. An effective and specific gRNA for the human P2RX2 V60L mutation has been identified. Our study establishes the feasibility of editing to treat DFNA41 caused by P2RX2 V60L mutation in humans and opens an avenue for using editing to rescue hearing and vestibular function while mitigating noise-induced hearing loss.

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Gene Editing Therapy Restores Hearing in Mice with Genetic Deafness

Abstract

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