AAV2.7m8 is a powerful viral vector for inner ear gene therapy

Kevin Isgrig, Devin S. McDougald, Jianliang Zhu, Hong Jun Wang, Jean Bennett and Wade W. Chien ()
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Kevin Isgrig: Neurotology Program, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health
Devin S. McDougald: Perelman School of Medicine, University of Pennsylvania
Jianliang Zhu: Neurotology Program, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health
Hong Jun Wang: Neurotology Program, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health
Jean Bennett: Perelman School of Medicine, University of Pennsylvania
Wade W. Chien: Neurotology Program, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health

Nature Communications, 2019, vol. 10, issue 1, 1-8

Abstract: Abstract Adeno-associated virus (AAV) has been successfully used to deliver gene therapy to improve auditory function in mouse models of hereditary hearing loss. Many forms of hereditary hearing loss have mutations which affect the cochlear hair cells, the mechanosensory cells which allow for sound detection and processing. While most conventional AAVs infect inner hair cells (IHCs) with various efficiencies, they infect outer hair cells (OHCs) and supporting cells at lower levels in the cochlea. Here we examine the infection patterns of two synthetic AAVs (AAV2.7m8 and AAV8BP2) in the mouse inner ear. AAV2.7m8 infects both IHCs and OHCs with high efficiency. In addition, AAV2.7m8 infects inner pillar cells and inner phalangeal cells with high efficiency. Our results suggest that AAV2.7m8 is an excellent viral vector for inner ear gene therapy targeting cochlear hair cells and supporting cells, and it will likely greatly expand the potential applications for inner ear gene therapy.

Date: 2019
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DOI: 10.1038/s41467-018-08243-1

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