Improving Editing Efficiency for the Sequences with NGH PAM Using xCas9-Derived Base Editors

doi:10.1016/j.omtn.2019.06.024

	Improving Editing Efficiency for the Sequences with NGH PAM Using xCas9-Derived Base Editors
	Liu, Xinyi 1; Li, Guanglei 2,3; Zhou, Xueliang 2,3; Qiao, Yunbo 4; Wang, Ruixuan5 ; Tang, Shaohui 6; Liu, Jianqiao 2,3; Wang, Lisheng 1; Huang, Xingxu5
	2019-09-06
发表期刊	MOLECULAR THERAPY-NUCLEIC ACIDS (IF:6.5[JCR-2023],6.7[5-Year])
ISSN	2162-2531
卷号	17 页码:626-635
发表状态	已发表
DOI	10.1016/j.omtn.2019.06.024
摘要	The development of CRISPR/Cas9-mediated base editors (BEs) provided a versatile tool for precise genome editing. The recently developed xCas9-derived base editors (xBEs) that recognize the NG PAM substantially expand the targeting scope in the genome, while their editing efficiency needs to be improved. Here, we described an improved version of xBEs by fusing the BPNLS and Gam to the N terminus of xBEs (BPNLS-Gam-xBE3 and BPNLS-xABE), and this version of base editor displayed higher targeting efficiency for the majority of detected sites. By using this improved version of xBEs, we successfully created and corrected pathogenic mutations at genomic sites with the NGN protospacer-adjacent motif in human cells. Lastly, we used BPNLS-Gam-xBE3 to model pathogenic mutations in discarded human tripronuclear (3PN) zygotes, and no obvious off-targets and indels were detected. Taken together, the data in our study offer an efficient tool for precise genome editing and, thus, an enriched base editing toolkit.
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收录类别	SCI ; SCIE
语种	英语
资助项目	China Postdoctoral Science Foundation[2019M650230]
WOS研究方向	Research & Experimental Medicine
WOS类目	Medicine, Research & Experimental
WOS记录号	WOS:000487984400055
出版者	CELL PRESS
WOS关键词	GENOMIC DNA ; IN-VITRO ; CAS9
原始文献类型	Article
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/80404
专题	生命科学与技术学院_硕士生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_博士生
通讯作者	Liu, Jianqiao; Wang, Lisheng; Huang, Xingxu
作者单位	1.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Gastroenterol, Shenzhen 510632, Peoples R China 2.Guangzhou Med Univ, Affiliated Hosp 3, Dept Reprod Med, Guangzhou 510150, Guangdong, Peoples R China 3.Guangzhou Med Univ, Affiliated Hosp 3, Key Lab Major Obstet Dis Guangdong Prov, Guangdong Higher Educ Inst,Key Lab Reprod & Genet, Guangzhou 510150, Guangdong, Peoples R China 4.Guangzhou Univ, Precise Genome Engn Ctr, Sch Life Sci, Guangzhou 510006, Guangdong, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 6.Jinan Univ, Affiliated Hosp 1, Dept Gastroenterol, Guangzhou 510632, Guangdong, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Liu, Xinyi,Li, Guanglei,Zhou, Xueliang,et al. Improving Editing Efficiency for the Sequences with NGH PAM Using xCas9-Derived Base Editors[J]. MOLECULAR THERAPY-NUCLEIC ACIDS,2019,17:626-635.
APA	Liu, Xinyi.,Li, Guanglei.,Zhou, Xueliang.,Qiao, Yunbo.,Wang, Ruixuan.,...&Huang, Xingxu.(2019).Improving Editing Efficiency for the Sequences with NGH PAM Using xCas9-Derived Base Editors.MOLECULAR THERAPY-NUCLEIC ACIDS,17,626-635.
MLA	Liu, Xinyi,et al."Improving Editing Efficiency for the Sequences with NGH PAM Using xCas9-Derived Base Editors".MOLECULAR THERAPY-NUCLEIC ACIDS 17(2019):626-635.