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

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2019,（2）
• 页码范围: 174-176
• 页数: 3页
• 语种: 英文

摘要

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.