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Sci Rep. 2017 Apr 3;7:45524. doi: 10.1038/srep45524.

Cochlear gene therapy with ancestral AAV in adult mice: complete transduction of inner hair cells without cochlear dysfunction.

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Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA.
Eaton-Peabody Laboratories, Massachusetts Eye &Ear Infirmary, Boston, MA 02114, USA.
Department of Otorhinolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan.
Grousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye &Ear Infirmary, Boston, MA 02114, USA.
Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.


The use of viral vectors for inner ear gene therapy is receiving increased attention for treatment of genetic hearing disorders. Most animal studies to date have injected viral suspensions into neonatal ears, via the round window membrane. Achieving transduction of hair cells, or sensory neurons, throughout the cochlea has proven difficult, and no studies have been able to efficiently transduce sensory cells in adult ears while maintaining normal cochlear function. Here, we show, for the first time, successful transduction of all inner hair cells and the majority of outer hair cells in an adult cochlea via virus injection into the posterior semicircular canal. We used a "designer" AAV, AAV2/Anc80L65, in which the main capsid proteins approximate the ancestral sequence state of AAV1, 2, 8, and 9. Our injections also transduced ~10% of spiral ganglion cells and a much larger fraction of their satellite cells. In the vestibular sensory epithelia, the virus transduced large numbers of hair cells and virtually all the supporting cells, along with close to half of the vestibular ganglion cells. We conclude that this viral vector and this delivery route hold great promise for gene therapy applications in both cochlear and vestibular sense organs.

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