Researchers at Seoul National University have developed a groundbreaking gene therapy that corrects a specific mutation in the MPZL2 gene, which is a primary cause of hereditary hearing loss, demonstrating promising potential for a one-time treatment.

The team created a humanized mouse model carrying the c.220C>T mutation in MPZL2, a common cause of DFNB11-type hereditary hearing loss in East Asian populations, which typically leads to rapid hearing decline after adolescence.

Using the advanced gene editing tool ABE8eWQ-SpRY, the researchers precisely converted adenine to guanine at the mutation site, achieving high accuracy with minimal damage to the DNA.

The gene editing components were delivered into the inner ear of mice via a single injection of an adeno-associated virus vector, resulting in significant hearing improvements of 20–30 dB across all frequencies, with effects lasting beyond 20 weeks.

Tissue analysis showed increased survival of auditory cells and structural recovery of cochlear tissue, indicating that gene correction contributed to both functional and structural restoration.

Safety assessments confirmed the high precision of the gene editing approach, with no off-target genetic effects detected through comprehensive DNA and RNA sequencing analyses.

This study marks the first demonstration of the preclinical therapeutic potential of Adenine Base Editor technology for hereditary hearing loss, highlighting its promise for future clinical applications.

Researchers emphasize that, unlike traditional treatments such as hearing aids or cochlear implants, this gene therapy offers a targeted solution for genetically caused hearing impairments and plan to move toward clinical trials.