Efficient base editing in G/C-rich regions to model androgen insensitivity syndrome
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 diseaserelated 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.
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We thank members of Huang lab,Sun lab,and Chen lab for helpful discussions.We are grateful to Dr.Tian Chi for excellent manuscript editing.This work is supported by the National Key R&D Program2016YFA0500903 and 2016YFC0905901;National Postdoctoral Program for Innovative TalentsBX201700266;Local Grants16JC1420200 and 17JC1420103;the Leading Talents of Guangdong Province2016LJ06S386
2019-03-26（万方平台首次上网日期，不代表论文的发表时间）
共3页
174-176
