A cytosine deaminase for programmable single-base RNA editing

Science. 2019 Jul 26;365(6451):382-386. doi: 10.1126/science.aax7063. Epub 2019 Jul 11.


Programmable RNA editing enables reversible recoding of RNA information for research and disease treatment. Previously, we developed a programmable adenosine-to-inosine (A-to-I) RNA editing approach by fusing catalytically inactivate RNA-targeting CRISPR-Cas13 (dCas13) with the adenine deaminase domain of ADAR2. Here, we report a cytidine-to-uridine (C-to-U) RNA editor, referred to as RNA Editing for Specific C-to-U Exchange (RESCUE), by directly evolving ADAR2 into a cytidine deaminase. RESCUE doubles the number of mutations targetable by RNA editing and enables modulation of phosphosignaling-relevant residues. We apply RESCUE to drive β-catenin activation and cellular growth. Furthermore, RESCUE retains A-to-I editing activity, enabling multiplexed C-to-U and A-to-I editing through the use of tailored guide RNAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / genetics
  • Adenosine Deaminase / chemistry
  • Adenosine Deaminase / genetics*
  • Cytidine / genetics*
  • Cytosine Deaminase / chemistry
  • Cytosine Deaminase / genetics*
  • HEK293 Cells
  • Humans
  • Inosine / genetics
  • Protein Domains
  • Protein Engineering / methods*
  • RNA Editing*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics*
  • Uridine / genetics*
  • beta Catenin / chemistry
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • CTNNB1 protein, human
  • RNA-Binding Proteins
  • beta Catenin
  • Inosine
  • Cytidine
  • Cytosine Deaminase
  • ADARB1 protein, human
  • Adenosine Deaminase
  • Adenosine
  • Uridine