详情页 - 四川省肿瘤医院知识库

当前位置：首页 > 详情页

In vivo base editing rescues photoreceptors in a mouse model of retinitis pigmentosa

文献详情

资源类型：

Pubmed体系：

作者：

机构： [1]Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, China [2]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China [3]Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China [4]Institute of Rare Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China

出处：

DOI：

ISSN：

摘要：

Retinitis pigmentosa (RP) is a group of retinal diseases that cause the progressive death of retinal photoreceptor cells and eventually blindness. Mutations in the β-domain of the phosphodiesterase 6 (Pde6b) gene are the most identified causes of autosomal recessive RP. Clinically, there is no effective treatment so far that can stop the progression of RP and restore the vision. Here, we report a base editing approach in which adeno-associated virus (AAV)-mediated adenine base editor (ABE) delivering to postmitotic photoreceptors was conducted to correct the Pde6b mutation in a retinal degeneration 10 (rd10) mouse model of RP. Subretinal delivery of AAV8-ABE corrected Pde6b mutation with averaging up to 20.79% efficiency at the DNA level and 54.97% efficiency at the cDNA level without bystanders, restored PDE6B expression, preserved photoreceptors, and rescued visual function. RNA-seq revealed the preservation of genes associated with phototransduction and photoreceptor survival. Our data have demonstrated that base editing is a potential gene therapy that could provide durable protection against RP.© 2023 The Author(s).

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2023]版：

大类 | 2 区

医学

小类 | 2 区医学：研究与实验

最新[2023]版：

大类 | 2 区

医学

小类 | 2 区医学：研究与实验

第一作者：

第一作者机构： [2]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China

共同第一作者：

通讯作者：

通讯机构： [1]Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, China [2]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China [*1]Department of Ophthalmology, West China Hospital, Sichuan University, Guoxue xiang, No.37, Chengdu, Sichuan 610041, China. [*2]Department of Ophthalmology, West China Hospital, Sichuan University, Ke-yuan Road 4, No. 1, Gao-peng Street, Chengdu, Sichuan 610041, China

推荐引用方式(GB/T 7714)：

APA：

MLA：