Gene-delivery therapy to restore hearing

The research team from Harvard Medical School (HMS) and the Massachusetts General Hospital (MGH) used the common AAV virus in their study to help restore hearing in a mouse model. AAV has already been used as a gene-delivery vehicle for retinal disorders, but thus far has proven much less effective in penetrating hair cells.

“To treat most forms of hearing loss, we need to find a delivery mechanism that works for all types of hair cells,” explains neurobiologist David Corey, co-senior investigator on the study and Professor of Translational Medical Science at HMS. To super-charge AAV as a gene carrier into the inner ear, the researchers used a form of the virus wrapped in protective bubbles called exosomes (exo-AAV).

“Unlike current approaches in the field, we didn’t change or directly modify the virus. Instead, we gave it a vehicle to travel in, making it better capable of navigating the terrain inside the inner ear and accessing previously resistant cells,” says co-investigator Casey Maguire, HMS Assistant Professor of neurology at MGH.

The group studied mice born without a gene critical for hair cell function; these are animals that normally cannot hear and have poor balance. After injecting exo-AAV preloaded with the missing gene into the inner ear of the test animals, the researchers found restored hearing in 9 of 12 mice and improvements in balance abilities, a sign of hair cell restoration.