Breakthrough AAV Gene Therapy Preserves Hearing and Balance in Animal Models

TEL AVIV— September 15, 2025—Scientists at Tel Aviv University, in collaboration with researchers from Boston Children’s Hospital and Harvard Medical School, have developed an innovative AAV gene therapy that successfully preserved hearing and balance in animal models with inner ear dysfunction. The new AAV treatment demonstrates enhanced efficiency over existing strategies and offers a promising path for treating a wide range of mutations that cause hearing loss.

The study, led by Prof. Karen Avraham and PhD student Roni Hahn, was featured on the cover of the journal EMBO Molecular Medicine. According to Prof. Avraham, the inner ear consists of two highly coordinated systems: the auditory system for sound and the vestibular system for balance. A wide range of genetic variants can affect these systems, with over half of congenital hearing loss cases caused by genetic factors.

A key component of the therapy is its use of an engineered AAV vector. “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,” explains Hahn. “These AAV vectors utilize the virus’s natural ability to enter cells to deliver the correct gene sequence, thereby restoring normal function.”

Specifically, the researchers investigated a mutation in the CLIC5 gene, which is crucial for maintaining the stability and function of hair cells in both the auditory and vestibular systems. Deficiency of this gene leads to progressive hair cell degeneration, resulting in hearing and balance problems.

The team utilized an advanced, structurally optimized version of the AAV vector, known as a self-complementary AAV (scAAV). This next-generation AAV vector achieved faster and more efficient transduction of hair cells, requiring a lower dose to achieve the therapeutic effect. In treated animal models, the AAV approach prevented hair cell degeneration and preserved normal hearing and balance.

Prof. Avraham believes these findings will pave the way for developing AAV gene therapies to treat a wide range of genetically caused hearing disorders.