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

Increased efficiency of base editing in methylated DNA using human APOBEC3A as a deaminase. 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.