Scientists in America have developed a one-time, gene editing treatment that restored hearing and balance in adult mice with a genetic form of hearing loss called DFNA41 which is also found in humans.
Dr Zheng-Yi Chen, senior author of the study and Associate Professor of Otolaryngology – Head and Neck Surgery at Harvard Medical School, said current gene therapy trials had been in children born with deafness.
“This study showed that our approach can be applied to patients who develop delayed onset hearing loss, from childhood to adulthood,” he said. “It showed for the first time, that precise gene editing can effectively treat dominant, progressive hearing loss in fully mature ears, bringing us closer to real-world applications in humans.”
Dr Chen said the research showed gene editing could be used as a one-time, lasting treatment to rescue hearing and balance in adults with genetic inner ear disorders, something previously thought to be possible only during early development.
The research found a single injection of the gene-editing therapy into the inner ear of adult mice with DFNA41 successfully and specifically disabled a harmful mutation in the P2RX2 gene while preserving the normal gene. Treating this mutation led to restored long-term hearing and balance in adult mice.
“We used a viral vector with a harmless adeno-associated virus (AAV) to deliver precise gene editing tools into the mouse inner ear,” he said.
“This editing specifically removed the harmful genetic mutation while keeping the healthy gene intact. As a result, the treated mice regained long-term hearing and balance. The gene editing treatment further protected mice from hypersensitivity to noise-induced hearing loss.”
Dr Chen said that in light of the team’s recent success using gene therapy to treat a different form of genetic hearing loss in children – autosomal deafness caused by mutations in the OTOF gene – (in one and both ears), the scientists believed this new work had the potential to become a treatment for patients with DFNA41.
Dr Chen is also associate scientist at the Eaton-Peabody Laboratories, and Ines and Fredrick Yeatts Chair in Otolaryngology, at Mass (Massachusetts) Eye and Ear hospital.
His paper was published in The Journal of Clinical Investigation on 14 August 2025.
“We were investigating whether a single-dose, gene editing therapy could safely and effectively correct a specific genetic mutation (P2RX2 V60L) that causes DFNA41, and whether this therapy could restore hearing in adult animal models, which better mimic human treatment conditions,” Dr Chen said.
“We wanted to find out if there is greater benefit if the intervention is carried out earlier. We also wanted to determine if this approach could protect against further damage from loud noise and vestibular dysfunction. These are crucial steps towards our ultimate goal of being able to safely translate this treatment to humans.”
Prevented further hearing loss from noise exposure
The study also showed the approach was safe by minimising risk factors such as off-target effect –the therapy affecting genes other than the specific one it targets.
A minimally invasive injection was delivered through the round window of the ear, a surgical delivery approach which has been successful in humans.
“We also found the therapy prevented further hearing loss caused by loud noise exposure,” Dr Chen said. “That finding is important because this increased hearing-loss risk from noise exposure is a known risk for DFNA41 patients.”
The team used a gene editing approach based on CRISPR-Cas9 technology and designed highly specific gene-editing tools.
“We verified editing accuracy and safety through genetic sequencing and tissue analysis by monitoring changes in hearing and balance over time using standard auditory and vestibular tests,” Dr Chen said.
“We also compared the treatment effects from the interventions at different time points.”
The research also demonstrated better treatment effects from early intervention, suggesting a similar strategy should be applied to humans.
“We were able to show this approach may have promise as a human treatment, as we identified an effective and specific editing strategy in patient-derived stem cells carrying the same human mutation (P2RX2 V60L),” Dr Chen said.
He said it laid the groundwork for first-in-human trials by showing safety, long-term benefit, and success in human stem cells carrying the same mutation. It may also be feasible for other forms of inherited deafness in adults, he added.
The team is now aiming to complete biodistribution and toxicity studies so they can initiate clinical trials in a few years.
