Researchers at the Gray Faculty of Medical and Health Sciences at Tel Aviv University (TAU) have introduced an innovative gene therapy method to treat impairments in hearing and balance caused by inner ear dysfunction. The treatment constitutes an improvement over existing strategies, demonstrating enhanced efficiency and holding promise for treating a wide range of mutations that cause hearing loss, the researchers say.

The study was led by Professor Karen Avraham, Dean of the Gray Faculty of Medical & Health Sciences, and Roni Hahn, a PhD student from the Department of Human Molecular Genetics and Biochemistry. The study was conducted in collaboration with Professor Jeffrey Holt and Dr. Gwenaëlle Géléoc from Boston Children’s Hospital and Harvard Medical School and was supported by the US-Israel Binational Science Foundation (BSF), the National Institutes of Health/NIDCD, and the Israel Science Foundation Breakthrough Research Program. The study was published on August 26, 2025, in the journal EMBO Molecular Medicine and was featured on its cover.

“The inner ear consists of two highly coordinated systems: the auditory system, which detects, processes, and transmits sound signals to the brain, and the vestibular system, which enables spatial orientation and balance,” Professor Avraham says. “A wide range of genetic variants in DNA can affect the function of these systems, leading to sensorineural hearing loss and balance problems.

“Indeed, hearing loss is the most common sensory impairment worldwide, with over half of congenital cases caused by genetic factors. In this study, we aimed to investigate an effective gene therapy for these cases using an approach that has not been applied in this context before.”

“Gene therapy has emerged as a powerful therapeutic approach in recent years and is now being applied to a range of genetic disorders, including spinal muscular atrophy (SMA) and Leber congenital amaurosis (LCA), as well as in cancer immunotherapy approaches such as CAR T-cell therapy,” Hahn continues. “One of the treatment strategies includes the use of engineered viral vectors, in which the native DNA is replaced with a functional sequence of the target gene. These vectors utilize the virus’s natural ability to enter cells to deliver the correct gene sequence, thereby restoring normal function.

“Many gene therapies utilize adeno-associated viruses (AAVs) to introduce therapeutic genetic material into target cells, and AAV-based gene therapy for hearing loss is currently in clinical trials, showing promising early results.”

The researchers investigated a mutation in the CLIC5 gene, which is essential for maintaining the stability and function of hair cells in the auditory and vestibular systems. Deficiency of this gene causes progressive degeneration of hair cells, initially leading to hearing loss and later resulting in balance problems.

The researchers utilized an advanced, structurally optimized version of the AAV vector, the self-complementary AAV (scAAV). They found that this vector achieved faster and more efficient transduction of hair cells compared to traditional AAV methods, requiring a lower dose to achieve a similar therapeutic effect. In animal models, this approach prevented hair cell degeneration and preserved normal hearing and balance.

“In this study, we applied an innovative treatment approach for genetic hearing loss and found that it improves therapeutic effectiveness while also addressing combined impairments in hearing and balance,” Professor Avraham concludes. “We anticipate that these findings will pave the way for developing gene therapies to treat a wide range of genetically caused hearing disorders.”