A precise and efficient adenine base editor

doi:10.1016/j.ymthe.2022.07.010

	A precise and efficient adenine base editor
	Tu, Tianxiang 1; Song, Zongming 2; Liu, Xiaoyu 1; Wang, Shengxing 3; He, Xiaoxue 1; Xi, Haitao ; Wang, Jiahua 1; Yan, Tong 1; Chen, Haoran 1; Zhang, Zhenwu5 ; Lv, Xiujuan 1; Lv, Jineng 1; Huang, Xiu-Feng ; Zhao, Junzhao 4; Lin, Chao-Po5 ; Gao, Caixia 3; Zhang, Jinwei 6; Gu, Feng 1
	2022-09-07
发表期刊	MOLECULAR THERAPY (IF:12.1[JCR-2023],11.8[5-Year])
ISSN	1525-0016
EISSN	1525-0024
卷号	30 期号:9
发表状态	已发表
DOI	10.1016/j.ymthe.2022.07.010
摘要	Adenine base editors (ABEs) are novel genome-editing tools, and their activity has been greatly enhanced by eight additional mutations, thus named ABE8e. However, elevated catalytic activity was concomitant with frequent generation of bystander mutations. This bystander effect precludes its safe applications required in human gene therapy. To develop next-generation ABEs that are both catalytically efficient and positionally precise, we performed combinatorial engineering of NG-ABE8e. We identify a novel variant (NG-ABE9e), which harbors nine mutations. NG-ABE9e exhibits robust and precise base-editing activity in human cells, with more than 7-fold bystander editing reduction at some sites, compared with NG-ABE8e. To demonstrate its practical utility, we used NG-ABE9e to correct the frequent T17M mutation in Rhodopsin for autosomal dominant retinitis pigmentosa. It reduces bystander editing by ,,,4-fold while maintaining comparable efficiency. NG-ABE9e possesses substantially higher activity than NG-ABEmax and significantly lower bystander editing than NG-ABE8e in rice. Therefore, this study provides a versatile and improved adenine base editor for genome editing.
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收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[81201181] ; National Key R&D Program of China[2018YFA 0107304] ; Science and Technology Project of Zhejiang Province[2017C37176] ; Wenzhou city grant[H20210011] ; Basic research project of Henan Eye Hospital[20JCZD001] ; Intramural Research Program of the NIH, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)[ZIADK075136]
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
WOS类目	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
WOS记录号	WOS:000860958400007
出版者	CELL PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/238141
专题	生命科学与技术学院_PI研究组_林照博组
通讯作者	Gao, Caixia; Zhang, Jinwei; Gu, Feng
作者单位	1.Wenzhou Med Univ, Eye Hosp, Sch Ophthalmol & Optometry, State Key Lab, Wenzhou, Zhejiang, Peoples R China 2.Zhengzhou Univ, Henan Univ, Henan Eye Hosp, Peoples Hosp,Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China 3.Chinese Acad Sci, Inst Genet & Dev Biol, Ctr Genome Editing, State Key Lab Plant Cell & Chromosome Engn, Beijing, Peoples R China 4.Wenzhou Med Univ, Yuying Childrens Hosp, Affiliated Hosp 2, Wenzhou, Zhejiang, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 6.NIH, Natl Inst Diabet & Digest & Kidney Dis, Lab Mol Biol, Bethesda, MD 20892 USA
推荐引用方式 GB/T 7714	Tu, Tianxiang,Song, Zongming,Liu, Xiaoyu,et al. A precise and efficient adenine base editor[J]. MOLECULAR THERAPY,2022,30(9).
APA	Tu, Tianxiang.,Song, Zongming.,Liu, Xiaoyu.,Wang, Shengxing.,He, Xiaoxue.,...&Gu, Feng.(2022).A precise and efficient adenine base editor.MOLECULAR THERAPY,30(9).
MLA	Tu, Tianxiang,et al."A precise and efficient adenine base editor".MOLECULAR THERAPY 30.9(2022).