“Landmark” Gene Therapy Work Significantly Restores Hearing in Genetically Deaf Mice

In the summer of 2015, a team at Boston Children's Hospital and Harvard Medical School reported restoring rudimentary hearing in genetically deaf mice using gene therapy. Now the Boston Children's research team reports restoring a much higher level of hearing -- down to 25 decibels, the equivalent of a whisper -- using an improved gene therapy vector developed at Massachusetts Eye and Ear. The new vector and the mouse studies are described in two back-to-back papers in Nature Biotechnology (published online on February 6, 2017). The first article is titled “A Synthetic AAV Vector Enables Safe and Efficient Gene Transfer to the Mammalian Inner Ear,” and the second is titled “Gene Therapy Restores Auditory and Vestibular Function in a Mouse Model of Usher Syndrome Type 1c.” While previous vectors have only been able to penetrate the cochlea's inner hair cells, the first Nature Biotechnology study showed that a new synthetic vector, Anc80, safely transferred genes to the hard-to-reach outer hair cells when introduced into the cochlea. This study's three Harvard Medical School senior investigators were Jeffrey R. Holt Ph.D., of Boston Children's Hospital; Konstantina Stankovic, M.D., Ph.D., of Massachusetts Eye and Ear and Luk H. Vandenberghe, Ph.D., who led Anc80's development in 2015 at Massachusetts Eye and Ear's Grousbeck Gene Therapy Center. "We have shown that Anc80 works remarkably well in terms of infecting cells of interest in the inner ear," says Stankovic, M.D., an otologic surgeon at Massachusetts Eye and Ear and Associate Professor of Otolaryngology at Harvard Medical School.