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Nat Biotechnol. 2017 Mar;35(3):264-272. doi: 10.1038/nbt.3801. Epub 2017 Feb 6.

Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c.

Author information

1
Department of Otolaryngology, F.M. Kirby Center for Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
2
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
3
Department of Cell Biology &Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, Chicago, Illinois, USA.
4
Department of Otorhinolaryngology &Bio-communications and Neuroscience Center, LSU Health Sciences Center, New Orleans, Louisiana, USA.
5
Department of Ophthalmology, Grousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.
6
Department of Neurology, F.M. Kirby Center for Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Because there are currently no biological treatments for hearing loss, we sought to advance gene therapy approaches to treat genetic deafness. We focused on Usher syndrome, a devastating genetic disorder that causes blindness, balance disorders and profound deafness, and studied a knock-in mouse model, Ush1c c.216G>A, for Usher syndrome type IC (USH1C). As restoration of complex auditory and balance function is likely to require gene delivery systems that target auditory and vestibular sensory cells with high efficiency, we delivered wild-type Ush1c into the inner ear of Ush1c c.216G>A mice using a synthetic adeno-associated viral vector, Anc80L65, shown to transduce 80-90% of sensory hair cells. We demonstrate recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders.

Comment in

PMID:
28165476
PMCID:
PMC5340578
DOI:
10.1038/nbt.3801
[Indexed for MEDLINE]
Free PMC Article

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