AAV-ie enables safe and efficient gene transfer to inner ear cells.

Nature communications (2019-08-21)
Fangzhi Tan, Cenfeng Chu, Jieyu Qi, Wenyan Li, Dan You, Ke Li, Xin Chen, Weidong Zhao, Cheng Cheng, Xiaoyi Liu, Yunbo Qiao, Bing Su, Shuijin He, Chao Zhong, Huawei Li, Renjie Chai, Guisheng Zhong

Hearing loss is the most common sensory disorder. While gene therapy has emerged as a promising treatment of inherited diseases like hearing loss, it is dependent on the identification of gene delivery vectors. Adeno-associated virus (AAV) vector-mediated gene therapy has been approved in the US for treating a rare inherited eye disease but no safe and efficient vectors have been identified that can target the diverse types of inner ear cells. Here, we identify an AAV variant, AAV-inner ear (AAV-ie), for gene delivery in mouse inner ear. Our results show that AAV-ie transduces the cochlear supporting cells (SCs) with high efficiency, representing a vast improvement over conventional AAV serotypes. Furthermore, after AAV-ie-mediated transfer of the Atoh1 gene, we find that many SCs trans-differentiated into new HCs. Our results suggest that AAV-ie is a useful tool for the cochlear gene therapy and for investigating the mechanism of HC regeneration.