AAV2.7m8 Is a Powerful Viral Vector for Inner Ear Gene Therapy

By June 7, 2019

Chien, Wade W.1,2; Isgrig, Kevin1; McDougald, Devin S.3; Zhu, Jianliang1; Wang, Hong Jun1; Bennett, Jean3
1 Neurotology Program, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health, Bethesda, Maryland, USA;
2 Department of Otolaryngology-Head & Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA;
3 Center for Advanced Retinal and Ocular Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Adeno-associated viruses (AAVs) are commonly used for inner ear gene delivery due to their excellent biosafety profiles. While conventional AAVs are capable of transducing inner hair cells (IHCs) in the cochlea to varying degrees, outer hair cells (OHCs) and supporting cells are transduced less efficiently. In order for AAVs to be useful for hair cell regeneration applications, they must be able of target the LGR5+ supporting cells that possess stem cell-like properties1,2. In this study, we show that AAV2.7m8 is capable of transducing the cochlear inner and outer hair cells as well as the LGR5+ supporting cells with high efficiency.

Neonatal (P0-P5) CBA/J mice were used in this study. AAV-GFPs were injected into mouse inner ear using the posterior semicircular canal approach. Immunohistochemistry was used to assess the infection efficiency.

AAV2.7m8 transduced both IHCs and OHCs with high efficiency. Comparison of IHC and OHC transduction of AAV2.7m8 with other AAVs (AAV2, AAV8, AAV8BP2, and Anc80L65) revealed that it is highly capable of transducing the cochlear IHCs and OHCs. AAV2.7m8 also transduced a subset of LGR5+ supporting cells (inner pillar cells and inner phalangeal cells) with high efficiency. Mice that underwent AAV2.7m8 injections had similar ABR thresholds and circling behavior compared to non-injected controls, indicating that it is a safe virus to use for inner ear gene therapy.

Our study showed that AAV2.7m8 transduced both IHCs and OHCs with high efficiency. Furthermore, AAV2.7m8 transduced the inner pillar cells and inner phalangeal cells with high efficiency, making AAV2.7m8 an excellent viral vector for hair cell regeneration applications.