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

Nat Biotechnol. 2018 Nov;36(10):946-949. doi: 10.1038/nbt.4198. Epub 2018 Aug 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • CRISPR-Associated Protein 9 / metabolism*
  • Cytidine Deaminase / genetics*
  • DNA / genetics
  • DNA Methylation
  • Gene Editing / methods*
  • HEK293 Cells
  • Humans
  • Mutagenesis, Site-Directed
  • Proteins / genetics*


  • Proteins
  • DNA
  • CRISPR-Associated Protein 9
  • APOBEC3A protein, human
  • Cytidine Deaminase