Usher syndrome (USH) is classified into three major clinical subtypes (types 1–3), with type 1 being the most severe. Usher syndrome type 1B (USH1B) is the most common form of USH Type 1 and is caused by a mutation in the MYO7A gene. USH1B patients are born with profound hearing loss, vestibular dysfunction (balance disorder), and progressive vision loss due to retinitis pigmentosa that begins within the first 10 years of life.
Recent advancements in gene therapy can address a genetic mutation by replacing the defective gene with a healthy copy. Viral vectors such as adeno-associated viruses (AAVs) are commonly used for gene delivery due to their safety (only inducing a mild immune response) and ability to infect a broad range of cells. However, AAVs can only carry (or package) up to 4.4Kb of DNA, and the MYO7A gene is ~6.7Kb. To work around this limitation, researchers at the National Institutes of Health (NIH) and the University of Florida split the healthy copy of MYO7A into two halves and inserted each half into separate AAV vectors for dual gene delivery of each half. When these two separate AAV vectors infect the same cell, the two halves join together to form a complete, healthy copy of the MYO7A gene with full functionality. Injection with dual-AAV delivery of MYO7A into a mouse model of USH1B restored MYO7A gene expression in both the cochlear and vestibular hair cells, leading to improved vestibular function.
What this means for Usher syndrome: Vestibular dysfunction puts USH1B patients at greater risk of falling and injury. Gene therapy treatment using this dual-AAV approach to repair the mutated MYO7A gene shows promise in helping USH1B patients lead safer lives.
