Correction of the pathogenic mutation in TGM1 gene by adenine base editing in mutant embryos

doi:10.1016/j.ymthe.2021.05.007

	Correction of the pathogenic mutation in TGM1 gene by adenine base editing in mutant embryos
	Dang, Lu 1; Zhou, Xueliang 1,2; Zhong, Xiufang 3; Yu, Wenxia4 ; Huang, Shisheng4 ; Liu, Hanyan 1,2; Chen, Yuanyuan 3; Zhang, Wuwen 3; Yuan, Lihua 3; Li, Lei 1,2; Huang, Xingxu4 ; Li, Guanglei4 ; Liu, Jianqiao 1,2; Tong, Guoqing 3
	2022-01-05
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:1
发表状态	已发表
DOI	10.1016/j.ymthe.2021.05.007
摘要	A couple diagnosed as carriers for lamellar ichthyosis, an autosomal recessive rare disease, encountered two pregnancy losses. Their blood samples showed the same heterozygous c.607C>T mutation in the TGM1 gene. However, we found that about 98.4% of the sperm had mutations, suggesting possible de novo germline mutation. To explore the probability of correcting this mutation, we used two different adenine base editors (ABEs) combined with related truncated single guide RNA (sgRNA) to repair the pathogenic mutation in mutant zygotes. Our results showed that the editing efficiency was 73.8% for ABEmax-NG combined with 20-bp-length sgRNA and 78.7% for Sc-ABEmax combined with 19-bp-length sgRNA. The whole-genome sequencing (WGS) and deep sequencing analysis demonstrated precise DNA editing. This study reveals the possibility of correcting the genetic mutation in embryos with the ABE system. © 2021 The American Society of Gene and Cell Therapy
关键词	adenine base editing correction mutant embryos pathogenic mutation TGM1 gene
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[81170571] ; National Key Research and Devel-opment Project[2018YFC1003803] ; Leading Talents of Guang-dong Province Program[608285568031]
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:000741619800020
出版者	Cell Press
原始文献类型	Journal article (JA)
Scopus 记录号	2-s2.0-85113456287
来源库	Scopus
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/128487
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
通讯作者	Li, Guanglei; Liu, Jianqiao; Tong, Guoqing
作者单位	1.Guangzhou Med Univ, Affiliated Hosp 3, Key Lab Major Obstetr Dis Guangdong Prov, Dept Obstet & Gynecol,Ctr Reprod Med, Guangzhou, Peoples R China 2.Guangzhou Med Univ, Affiliated Hosp 3, Key Lab Reprod Med Guangdong Prov, Guangzhou, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Reprod Ctr, Shanghai 201203, Peoples R China 4.ShanghaiTech Univ, Gene Editing Ctr, Sch Life Sci & Technol, Shanghai 201210, 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	Dang, Lu,Zhou, Xueliang,Zhong, Xiufang,et al. Correction of the pathogenic mutation in TGM1 gene by adenine base editing in mutant embryos[J]. MOLECULAR THERAPY,2022,30(1).
APA	Dang, Lu.,Zhou, Xueliang.,Zhong, Xiufang.,Yu, Wenxia.,Huang, Shisheng.,...&Tong, Guoqing.(2022).Correction of the pathogenic mutation in TGM1 gene by adenine base editing in mutant embryos.MOLECULAR THERAPY,30(1).
MLA	Dang, Lu,et al."Correction of the pathogenic mutation in TGM1 gene by adenine base editing in mutant embryos".MOLECULAR THERAPY 30.1(2022).