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

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...

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Autores principales: Tan, Fangzhi, Chu, Cenfeng, Qi, Jieyu, Li, Wenyan, You, Dan, Li, Ke, Chen, Xin, Zhao, Weidong, Cheng, Cheng, Liu, Xiaoyi, Qiao, Yunbo, Su, Bing, He, Shuijin, Zhong, Chao, Li, Huawei, Chai, Renjie, Zhong, Guisheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700137/
https://www.ncbi.nlm.nih.gov/pubmed/31427575
http://dx.doi.org/10.1038/s41467-019-11687-8
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author Tan, Fangzhi
Chu, Cenfeng
Qi, Jieyu
Li, Wenyan
You, Dan
Li, Ke
Chen, Xin
Zhao, Weidong
Cheng, Cheng
Liu, Xiaoyi
Qiao, Yunbo
Su, Bing
He, Shuijin
Zhong, Chao
Li, Huawei
Chai, Renjie
Zhong, Guisheng
author_facet Tan, Fangzhi
Chu, Cenfeng
Qi, Jieyu
Li, Wenyan
You, Dan
Li, Ke
Chen, Xin
Zhao, Weidong
Cheng, Cheng
Liu, Xiaoyi
Qiao, Yunbo
Su, Bing
He, Shuijin
Zhong, Chao
Li, Huawei
Chai, Renjie
Zhong, Guisheng
author_sort Tan, Fangzhi
collection PubMed
description 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.
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spelling pubmed-67001372019-08-21 AAV-ie enables safe and efficient gene transfer to inner ear cells Tan, Fangzhi Chu, Cenfeng Qi, Jieyu Li, Wenyan You, Dan Li, Ke Chen, Xin Zhao, Weidong Cheng, Cheng Liu, Xiaoyi Qiao, Yunbo Su, Bing He, Shuijin Zhong, Chao Li, Huawei Chai, Renjie Zhong, Guisheng Nat Commun Article 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. Nature Publishing Group UK 2019-08-19 /pmc/articles/PMC6700137/ /pubmed/31427575 http://dx.doi.org/10.1038/s41467-019-11687-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Tan, Fangzhi
Chu, Cenfeng
Qi, Jieyu
Li, Wenyan
You, Dan
Li, Ke
Chen, Xin
Zhao, Weidong
Cheng, Cheng
Liu, Xiaoyi
Qiao, Yunbo
Su, Bing
He, Shuijin
Zhong, Chao
Li, Huawei
Chai, Renjie
Zhong, Guisheng
AAV-ie enables safe and efficient gene transfer to inner ear cells
title AAV-ie enables safe and efficient gene transfer to inner ear cells
title_full AAV-ie enables safe and efficient gene transfer to inner ear cells
title_fullStr AAV-ie enables safe and efficient gene transfer to inner ear cells
title_full_unstemmed AAV-ie enables safe and efficient gene transfer to inner ear cells
title_short AAV-ie enables safe and efficient gene transfer to inner ear cells
title_sort aav-ie enables safe and efficient gene transfer to inner ear cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700137/
https://www.ncbi.nlm.nih.gov/pubmed/31427575
http://dx.doi.org/10.1038/s41467-019-11687-8
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