TY - JOUR
T1 - AAV-ie enables safe and efficient gene transfer to inner ear cells
AU - Tan, Fangzhi
AU - Chu, Cenfeng
AU - Qi, Jieyu
AU - Li, Wenyan
AU - You, Dan
AU - Li, Ke
AU - Chen, Xin
AU - Zhao, Weidong
AU - Cheng, Cheng
AU - Liu, Xiaoyi
AU - Qiao, Yunbo
AU - Su, Bing
AU - He, Shuijin
AU - Zhong, Chao
AU - Li, Huawei
AU - Chai, Renjie
AU - Zhong, Guisheng
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071016152&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-11687-8
DO - 10.1038/s41467-019-11687-8
M3 - Article
C2 - 31427575
AN - SCOPUS:85071016152
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3733
ER -