Efficient base editing in methylated regions with a human APOBEC3A-Cas9 fusion.

Wang, Xiao; Li, Jianan; Wang, Ying; Yang, Bei; Wei, Jia; Wu, Jing; Wang, Ruixuan; Huang, Xingxu et al. · Nat Biotechnol · 2018

basic_science · Level V

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Abstract

Base editors (BEs) enable the generation of targeted single-nucleotide mutations, but currently used rat APOBEC1-based BEs are relatively inefficient in editing cytosines in highly methylated regions or in GpC contexts. By screening a variety of APOBEC and AID deaminases, we show that human APOBEC3A-conjugated BEs and versions we engineered to have narrower editing windows can mediate efficient C-to-T base editing in regions with high methylation levels and GpC dinucleotide content.

Medical subject headings