Engineering of near-PAMless adenine base editor with enhanced editing activity and reduced off-target

doi:10.1016/j.omtn.2022.04.032

	Engineering of near-PAMless adenine base editor with enhanced editing activity and reduced off-target
	Cao, Xiaofang 1,2,3; Guo, Junfan4,5 ; Huang, Shisheng4,5 ; Yu, Wenxia4,5 ; Li, Guanglei4 ; An, Lisha 1,3; Li, Xiangyang4,5 ; Tao, Wanyu4,5 ; Liu, Qing 6; Huang, Xingxu4 ; Jin, Xiaohua 1,2,3; Ma, Xu 1,2,3
	2022-06-14
发表期刊	MOLECULAR THERAPY-NUCLEIC ACIDS (IF:6.5[JCR-2023],6.7[5-Year])
ISSN	2162-2531
卷号	28
发表状态	已发表
DOI	10.1016/j.omtn.2022.04.032
摘要	About 47% of pathogenic point mutations could be corrected by ABE-induced A.T-to-G.C conversions. However, the applications of ABEs are still hindered by undesired editing efficiency, limited editing scopes, and off-targeting effects. Here, we develop a new adenine base editor, by embedding TadA-8e monomer into SpRY-nCas9, named as CE-8e-SpRY, which exhibits higher activity at NRN than NYN PAMs favored by SpRY nuclease. CE-8e-SpRY could target nearly all genomic sites in principle and induces the highest targeting efficiency among tested SpRY-based ABEs. In addition, CE-8e-SpRY also shows reduced RNA and DNA off-targeting activities. With optimized sgRNAs, CE-8e-SpRY induces efficient or desired target editing at some disease-relevant loci where conventional ABEs were unable to induce precise and satisfied editing. Taken together, our CE-8e-SpRY could broaden the applicability of ABEs in correcting or introducing pathogenic point mutations.
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
资助项目	National Key Research and Development Program of China[2016YFC1000307] ; Leading Talents of Guangdong Province Program[608285568031]
WOS研究方向	Research & Experimental Medicine
WOS类目	Medicine, Research & Experimental
WOS记录号	WOS:000835333400005
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/226383
专题	生命科学与技术学院_博士生生命科学与技术学院_PI研究组_池天组生命科学与技术学院_PI研究组_黄行许组生命科学与技术学院_硕士生
共同第一作者	Guo, Junfan
通讯作者	Jin, Xiaohua; Ma, Xu
作者单位	1.Natl Res Inst Family Planning, Beijing 100081, Peoples R China 2.Chinese Acad Med Sci, Grad Sch, Peking Union Med Coll, Beijing 100005, Peoples R China 3.Natl Human Genet Resources Ctr, Beijing 102206, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Southern Med Univ, Sch Basic Med Sci, Dept Med Genet, Guangzhou 510515, Peoples R China
推荐引用方式 GB/T 7714	Cao, Xiaofang,Guo, Junfan,Huang, Shisheng,et al. Engineering of near-PAMless adenine base editor with enhanced editing activity and reduced off-target[J]. MOLECULAR THERAPY-NUCLEIC ACIDS,2022,28.
APA	Cao, Xiaofang.,Guo, Junfan.,Huang, Shisheng.,Yu, Wenxia.,Li, Guanglei.,...&Ma, Xu.(2022).Engineering of near-PAMless adenine base editor with enhanced editing activity and reduced off-target.MOLECULAR THERAPY-NUCLEIC ACIDS,28.
MLA	Cao, Xiaofang,et al."Engineering of near-PAMless adenine base editor with enhanced editing activity and reduced off-target".MOLECULAR THERAPY-NUCLEIC ACIDS 28(2022).