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Engineered IscB-WRNA system with improved base editing efficiency for disease correction via single AAV delivery in mice

文献类型：期刊论文

作者Guo, Ruochen6,7; Sun, Xiaozhi1,6; Wang, Feizuo2; Han, Dingyi7; Yang, Qiaoxia3; Gao, Hua1,6; Li, Zhifang6; Shao, Zhuang6; Shi, Jinqi6; Yang, Rongrong4,6
刊名CELL REPORTS
出版日期2024-11-26
卷号43期号:11页码:18
ISSN号2211-1247
DOI10.1016/j.celrep.2024.114973
通讯作者Wang, Leyun(wangleyun@xmu.edu.cn) ; Hu, Chunyi(hu_dbs@nus.edu.sg) ; Xu, Chunlong(xucl@lglab.ac.cn)
英文摘要IscBs, as hypercompact ancestry proteins of Cas9 nuclease, are suitable for in vivo gene editing via single adeno-associated virus (AAV) delivery. Due to the low activity of natural IscBs in eukaryotic cells, recent studies have been focusing on improving OgeuIscB's gene editing efficiency via protein engineering. However, in vivo gene editing efficacy of IscBs for disease correction remained to be demonstrated. Here, we showed effective gene knockout and base editing in mouse embryos. To further improve IscB activity, we performed systematic engineering of IscB-associated WRNA and identified a variant, WRNA*-v2, with enhanced gene editing efficiency. Furthermore, our study demonstrated the efficacy of an engineered IscB-WRNA system for robust gene knockout and base editing in vivo. Single AAV delivery of IscB-derived cytosine and adenine base editors achieved disease correction in a mouse model of tyrosinemia. Therefore, our results indicated the great potential of miniature IscBs for developing single-AAV-based gene editing therapeutics.
WOS关键词FUMARYLACETOACETATE HYDROLASE GENE ; MUTATIONS
资助项目Lingang Laboratory ; Shanghai City Committee of Science and Technology Project[22QA1412300] ; Shanghai City Committee of Science and Technology Project[20ZR1466600]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:001357275900001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/314542]  
专题中国科学院上海药物研究所
通讯作者Wang, Leyun; Hu, Chunyi; Xu, Chunlong
作者单位1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
2.Natl Univ Singapore, Dept Biol Sci, Dept Biochem, Precis Med Translat Res Programme TRP, Singapore, Singapore
3.Xiamen Univ, Xiamen Cardiovasc Hosp, Fac Med & Life Sci, Sch Med,Dept Obstet & Gynecol,Xiamen Key Lab Cardi, Xiamen, Fujian, Peoples R China
4.Shanghai Ctr Brain Sci & Brain Inspired Technol, Shanghai, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
6.Lingang Lab, Shanghai, Peoples R China
7.Chinese Acad Sci, Inst Neurosci, Shanghai Inst Biol Sci, Ctr Excellence Brain Sci & Intelligence Technol,Ke, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Guo, Ruochen,Sun, Xiaozhi,Wang, Feizuo,et al. Engineered IscB-WRNA system with improved base editing efficiency for disease correction via single AAV delivery in mice[J]. CELL REPORTS,2024,43(11):18.
APA Guo, Ruochen.,Sun, Xiaozhi.,Wang, Feizuo.,Han, Dingyi.,Yang, Qiaoxia.,...&Xu, Chunlong.(2024).Engineered IscB-WRNA system with improved base editing efficiency for disease correction via single AAV delivery in mice.CELL REPORTS,43(11),18.
MLA Guo, Ruochen,et al."Engineered IscB-WRNA system with improved base editing efficiency for disease correction via single AAV delivery in mice".CELL REPORTS 43.11(2024):18.

入库方式： OAI收割

来源：上海药物研究所

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