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Volume 29, No 2, Feb 2019

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 29 Issue 2, February 2019: 174-176

LETTERS TO THE EDITOR

Efficient base editing in G/C-rich regions to model androgen insensitivity syndrome

Jianan Li 1,2,3, Zhen Liu 4, Shisheng Huang 1,2,3, Xiao Wang 1,2,3, Guanglei Li 1,5, Yuting Xu 4, Wenxia Yu 1,2,3, Shanshan Chen 4, Yu Zhang 1, Hanhui Ma 1, Zunfu Ke 6, Jia Chen 1,7, Qiang Sun 4 and Xingxu Huang 1,7

1 School of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China; 2 Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 200031 Shanghai, China; 3 University of Chinese Academy of Sciences, 100049 Beijing, China;4Institute of Neuroscience, Chinese Academy of Sciences (CAS) Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 200031 Shanghai, China; 5 International Academy of Optoelectronics at Zhaoqing, South China Normal University, 526060 Guangdong, China; 6 Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080 Guangdong, China and 7 CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 200031 Shanghai, China
These authors contributed equally: Jianan Li, Zhen Liu, Shisheng
Huang Correspondence: Correspondence: Jia Chen (chenjia@shanghaitech.edu.cn) or Qiang Sun (qsun@ion.ac.cn) or Xingxu Huang (huangxx@shanghaitech.edu.cn)

Dear Editor,

Most disease-associated genomic mutations are base substitutions and approximately half of pathogenic human single nucleotide polymorphisms (SNPs) are related to C-to-T substitutions in the ClinVar database.1 Base editors (BEs), which combine Cas9-D10A nickase and APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) or AID (activation-induced deaminase) cytidine deaminase family members,2 have been successfully applied to mediate C-to-T conversion in vitro and in vivo,3 providing a powerful tool to model or repair disease-related human SNPs. Yet, the editing scope of BE3 was limited by the low editing efficiency at GpC dinucleotides and/or in regions with high CpG methylation levels.2 We recently replaced rA1 with human APOBEC3A (hA3A) and then engineered hA3A isoform to develop a series of hA3A-BEs, including hA3A-BE3-Y130F, which has an editing window similar to BE3.4 As hA3A can deaminate both C and methylated C in various sequence contexts efficiently,5 hA3A-BE3-Y130F mediated efficient C-to-T base editing in GpC context and CpG context in vitro.4


https://doi.org/10.1038/s41422-018-0133-4

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