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    Gene therapy restores hearing in mice

    Unaffected mice, at left, have sensory hair bundles organized in 'V' formations with three rows of cilia (bottom left). This orderly structure falls apart in the mutant mice (middle column), but is dramatically restored after gene therapy treatment.

    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 February 6).

    People with Usher syndrome type I have genetic mutations that cause deafness in childhood, progressive blindness and balance disorders. Gwenaëlle Géléoc at Boston Children's Hospital in Massachusetts and her colleagues studied newborn mice with a form of Usher syndrome type I. They injected a synthetic virus that carried a healthy version of the gene for a protein called harmonin into the animal's' ears. The protein resides in sound-sensitive 'hair' cells of the inner ear and helps to transmit auditory signals to the brain. The team found that mice given the gene responded to sounds as quiet as whispers, similarly to normal mice. The treated mice also performed as well in balance tests as normal mice.

    While previous vectors have only been able to penetrate the cochlea's inner hair cells, Luk Vandenberghe at the Schepens Eye Research Institute of Massachusetts Eye and Ear in Boston and his colleagues discovered that a new synthetic vector, Anc80, safely transferred genes to the hard-to-reach outer hair cells when introduced into the cochlea (see images). In the second Nature Biotechnology study, they showed that the same virus delivered genes to a large number of the target hair cells in the mouse ear.

    "We have shown that Anc80 works remarkably well in terms of infecting cells of interest in the inner ear," says Stankovic, an otologic surgeon at Mass. Eye and Ear and associate professor of otolaryngology at Harvard Medical School. "With more than 100 genes already known to cause deafness in humans, there are many patients who may eventually benefit from this technology."

    Read more:

    Landegger et al. A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear. Nature Biotechnology (2017)

    Pan et al. Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c. Nature Biotechnology (2017)