An improved gene therapy vector restores hearing and balance in genetically deaf mice, according to Boston’s Children’s Hospital researchers. Using therapy developed by Massachusetts Eye and Ear, the mice’s levels of hearing are reported to be able to detect sounds as soft as 25 decibels, which is comparable to a whisper.

Share on Pinterest Hair cells in mice with a genetic mutation are restored to “V” formations following gene therapy treatment.

Image credit: Gwenaelle Géléoc and Artur Indzkykulian



The idea of gene therapy is to deliver a corrected version of therapeutic DNA into the genomes of cells, which corrects genetic diseases.

Viruses can be altered in a laboratory to provide a “vector” that can carry the corrected therapeutic DNA into the cells. The abnormal gene expression is then altered, and the genetic disease corrected.

Previous studies have used vectors to attempt the restoration of hearing among deaf mice. However, the vectors have only managed to penetrate the inner hair cells of the cochlea.

The cochlea is a spiral-shaped tube that changes sounds to nerve messages and sends the information to the brain. Tiny hairs in the cochlea vibrate to carry information about sound to the brain.

Two new studies, published in Nature Biotechnology, have further explored vectors in mice to determine whether other hair cells of the cochlea, which are harder to reach, could be penetrated and corrected.

The first study was led by Harvard Medical School senior investigators Jeffrey R. Holt, Ph.D., of Boston’s Children’s Hospital in Massachusetts, Konstantina Stankovic, Ph.D., of Massachusetts Eye and Ear, and Luk H. Vandenberghe, Ph.D. The trio developed a new synthetic vector called Anc80 in 2015 at Massachusetts Eye and Ear’s Grousbeck Gene Therapy Center.

The new study found that Anc80 could successfully transfer genes to the harder-to-reach areas of the outer hair cells when introduced into the cochlea. “We have shown that Anc80 works remarkably well in terms of infecting cells of interest in the inner ear,” says Stankovic. “With more than 100 genes already known to cause deafness in humans, there are many patients who may eventually benefit from this technology.”

Gwenaëlle Géléoc, Ph.D., of the department of otolaryngology and F.M. Kirby Neurobiology Center at Boston’s Children’s Hospital, led the second study. The study tested Anc80 in a mouse model of Usher syndrome. Usher syndrome is a genetic condition caused by abnormalities of the inner ear. The condition causes partial or total hearing and vision loss that becomes worse over time, eventually impairing balance.

Géléoc and colleagues aimed to find out whether delivering a corrected gene using a vector in a mouse model of Usher syndrome would enhance hearing and balance.

“This strategy is the most effective one we’ve tested,” says Géléoc. “Outer hair cells amplify sound, allowing inner hair cells to send a stronger signal to the brain. We now have a system that works well and rescues auditory and vestibular function to a level that’s never been achieved before,” she adds.