AAV-ie-K558R mediated cochlear gene therapy and hair cell regeneration

doi:10.1038/s41392-022-00938-8

	AAV-ie-K558R mediated cochlear gene therapy and hair cell regeneration
	Tao, Yong 1,2,3; Liu, Xiaoyi4,5 ; Yang, Liu4,5 ; Chu, Cenfeng4,5 ; Tan, Fangzhi4,5 ; Yu, Zehua4,5 ; Ke, Junzi4,5 ; Li, Xiang 1,2,3; Zheng, Xiaofei 1,2,3; Zhao, Xingle 1,2,3; Qi, Jieyu 6,7; Lin, Chao Po 5; Chai, Renjie 6,7,8,9; Zhong, Guisheng1,4,5 ; Wu, Hao 1,2,3
	2022-04-22
发表期刊	SIGNAL TRANSDUCTION AND TARGETED THERAPY
ISSN	2095-9907
EISSN	2059-3635
卷号	7 期号:1
发表状态	已发表
DOI	10.1038/s41392-022-00938-8
摘要	The cochlea consists of multiple types of cells, including hair cells, supporting cells and spiral ganglion neurons, and is responsible for converting mechanical forces into electric signals that enable hearing. Genetic and environmental factors can result in dysfunctions of cochlear and auditory systems. In recent years, gene therapy has emerged as a promising treatment in animal deafness models. One major challenge of the gene therapy for deafness is to effectively deliver genes to specific cells of cochleae. Here, we screened and identified an AAV-ie mutant, AAV-ie-K558R, that transduces hair cells and supporting cells in the cochleae of neonatal mice with high efficiency. AAV-ie-K558R is a safe vector with no obvious deficits in the hearing system. We found that AAV-ie-K558R can partially restore the hearing loss in Prestin KO mice and, importantly, deliver Atoh1 into cochlear supporting cells to generate hair cell-like cells. Our results demonstrate the clinical potential of AAV-ie-K558R for treating the hearing loss caused by hair cell death.
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收录类别	SCI ; SCIE
语种	英语
资助项目	Key Project of the National Natural Science Foundation of China[NSFC 81730028] ; National Key Technology Research and Development Program of the Ministry of Science and Technology of China[2017YFC1001800] ; Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases[14DZ2260300] ; Shanghai Municipal Science and Technology Major Project[2018SHZDZX05] ; National Natural Science Foundation of China[31771130,82122019]
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000784713200001
出版者	SPRINGERNATURE
Scopus 记录号	2-s2.0-85128669313
来源库	Scopus
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/176041
专题	生命科学与技术学院_硕士生 iHuman研究所_PI研究组_钟桂生组生命科学与技术学院_博士生
通讯作者	Chai, Renjie; Zhong, Guisheng; Wu, Hao
作者单位	1.Department of Otolaryngology-Head and Neck Surgery,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200011,China 2.Ear Institute,Shanghai Jiao Tong University School of Medicine,Shanghai,200011,China 3.Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases,Shanghai,200011,China 4.iHuman Institute,ShanghaiTech University,Shanghai,201210,China 5.School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China 6.State Key Laboratory of Bioelectronics,Department of Otolaryngology Head and Neck Surgery,Zhongda Hospital,School of Life Sciences and Technology,Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research,Southeast University,Nanjing,210096,China 7.Co-Innovation Center of Neuroregeneration,Nantong University,Nantong,226001,China 8.Institute for Stem Cell and Regeneration,Chinese Academy of Science,Beijing,China 9.Beijing Key Laboratory of Neural Regeneration and Repair,Capital Medical University,Beijing,100069,China
通讯作者单位	iHuman研究所; 生命科学与技术学院
推荐引用方式 GB/T 7714	Tao, Yong,Liu, Xiaoyi,Yang, Liu,et al. AAV-ie-K558R mediated cochlear gene therapy and hair cell regeneration[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2022,7(1).
APA	Tao, Yong.,Liu, Xiaoyi.,Yang, Liu.,Chu, Cenfeng.,Tan, Fangzhi.,...&Wu, Hao.(2022).AAV-ie-K558R mediated cochlear gene therapy and hair cell regeneration.SIGNAL TRANSDUCTION AND TARGETED THERAPY,7(1).
MLA	Tao, Yong,et al."AAV-ie-K558R mediated cochlear gene therapy and hair cell regeneration".SIGNAL TRANSDUCTION AND TARGETED THERAPY 7.1(2022).