Development of a versatile nuclease prime editor with upgraded precision

doi:org/10.1038/s41467-023-35870-0

	Development of a versatile nuclease prime editor with upgraded precision
	Li, Xiangyang1,2 ; Zhang, Guiquan 2,3; Huang, Shisheng 2; Liu, Yao 4; Tang, Jin 2; Zhong, Mingtian 5; Wang, Xin1 ; Sun, Wenjun1 ; Yao, Yuan 6,7; Ji, Quanjiang8 ; Wang, Xiaolong 4; Liu, Jianghuai 3; Zhu, Shiqiang 2; Huang, Xingxu1,2
	2023-01
发表期刊	NATURE COMMUNICATION (IF:14.7[JCR-2023],16.1[5-Year])
ISSN	2041-1723
EISSN	2041-1723
卷号	12 期号:1 页码:305
发表状态	已发表
DOI	org/10.1038/s41467-023-35870-0
摘要	["The applicability of nuclease-based form of prime editor (PEn) has been hindered by its complexed editing outcomes. A chemical inhibitor against DNA-PK, which mediates the nonhomologous end joining (NHEJ) pathway, was recently shown to promote precise insertions by PEn. Nevertheless, the intrinsic issues of specificity and toxicity for such a chemical approach necessitate development of alternative strategies. Here, we find that co-introduction of PEn and a NHEJ-restraining, 53BP1-inhibitory ubiquitin variant potently drives precise edits via mitigation of unintended edits, framing a high-activity editing platform (uPEn) apparently complementing the canonical PE. Further developments involve exploring the effective configuration of a homologous region-containing pegRNA (HR-pegRNA). Overall, uPEn can empower high-efficiency installation of insertions (38%), deletions (43%) and replacements (52%) in HEK293T cells. When compared with PE3/5max, uPEn demonstrates superior activities for typically refractory base substitutions, and for small-block edits. Collectively, this work establishes a highly efficient PE platform with broad application potential.","Strategies to improve the specificity of nuclease-based prime editor (PEn) are needed. Here the authors report a 53BP1-inhibitory ubiquitin variant-assisted PEn platform (uPEn) to inhibit NHEJ and enable precise prime editing for generation of insertions, deletions and replacements."]
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收录类别	SCI
语种	英语
资助项目	National Key R & D Program of China["2021YFF1000704","2021YFA0804702"] ; Key Research Project of Zhejiang Laboratory[2021PE0AC06] ; Leading Talents of Guangdong Province Program[2016LJ06S386]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000982581400010
出版者	NATURE PORTFOLIO
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/279729
专题	生命科学与技术学院物质科学与技术学院生命科学与技术学院_PI研究组_黄行许组物质科学与技术学院_PI研究组_季泉江组生命科学与技术学院_博士生
通讯作者	Liu, Jianghuai; Zhu, Shiqiang; Huang, Xingxu
作者单位	1.ShanghaiTech Univ, Gene Editing Ctr, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 2.Zhejiang Lab, Hangzhou 311121, Zhejiang, Peoples R China 3.Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Model Anim Res Ctr, Med Sch, Nanjing 210061, Peoples R China 4.Northwest A&F Univ, Coll Anim Sci & Technol, Key Lab Anim Genet Breeding & Reprod Shaanxi Prov, Yangling 712100, Shaanxi, Peoples R China 5.South China Normal Univ, Inst Brain Res & Rehabil, Guangzhou 510631, Peoples R China 6.Zhejiang Univ, ZJU Hangzhou Global Sci & Technol Innovat Ctr, Hangzhou 311215, Peoples R China 7.Zhejiang Univ, Coll Chem & Biol Engn, Hangzhou 310027, Peoples R China 8.ShanghaiTech Univ, Sch Phys Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Li, Xiangyang,Zhang, Guiquan,Huang, Shisheng,et al. Development of a versatile nuclease prime editor with upgraded precision[J]. NATURE COMMUNICATION,2023,12(1):305.
APA	Li, Xiangyang.,Zhang, Guiquan.,Huang, Shisheng.,Liu, Yao.,Tang, Jin.,...&Huang, Xingxu.(2023).Development of a versatile nuclease prime editor with upgraded precision.NATURE COMMUNICATION,12(1),305.
MLA	Li, Xiangyang,et al."Development of a versatile nuclease prime editor with upgraded precision".NATURE COMMUNICATION 12.1(2023):305.