Adenine base editors catalyze cytosine conversions in human cells

Nat Biotechnol. 2019 Oct;37(10):1145-1148. doi: 10.1038/s41587-019-0254-4. Epub 2019 Sep 23.

Abstract

Adenine base editors comprise an adenosine deaminase, evolved in vitro, and a Cas9 nickase. Here, we show that in addition to converting adenine to guanine, adenine base editors also convert cytosine to guanine or thymine in a narrow editing window (positions 5-7) and in a confined TC*N sequence context. Adenine base editor-induced cytosine substitutions occur independently of adenosine conversions with an efficiency of up to 11.2% and reduce the number of suitable targeting sites for high-specificity base editing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminohydrolases / metabolism*
  • CRISPR-Associated Protein 9*
  • Cell Line
  • Deoxyribonuclease I / metabolism*
  • Gene Editing / methods*
  • Humans

Substances

  • CRISPR-Associated Protein 9
  • Deoxyribonuclease I
  • Aminohydrolases
  • adenine deaminase