Adenine base editing in an adult mouse model of tyrosinaemia

Nat Biomed Eng. 2020 Jan;4(1):125-130. doi: 10.1038/s41551-019-0357-8. Epub 2019 Feb 25.


In contrast to traditional CRISPR-Cas9 homology-directed repair, base editing can correct point mutations without supplying a DNA-repair template. Here we show in a mouse model of tyrosinaemia that hydrodynamic tail-vein injection of plasmid DNA encoding the adenine base editor (ABE) and a single-guide RNA (sgRNA) can correct an A>G splice-site mutation. ABE treatment partially restored splicing, generated fumarylacetoacetate hydrolase (FAH)-positive hepatocytes in the liver, and rescued weight loss in mice. We also generated FAH+ hepatocytes in the liver via lipid-nanoparticle-mediated delivery of a chemically modified sgRNA and an mRNA of a codon-optimized base editor that displayed higher base-editing efficiency than the standard ABEs. Our findings suggest that adenine base editing can be used for the correction of genetic diseases in adult animals.

Publication types

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

MeSH terms

  • Adenine / metabolism*
  • Animals
  • Disease Models, Animal
  • Female
  • Gene Editing / methods*
  • HEK293 Cells
  • Hepatocytes / metabolism
  • Humans
  • Hydrolases / genetics
  • Liver / metabolism
  • Point Mutation
  • RNA / administration & dosage
  • Tyrosinemias / genetics*


  • RNA
  • Hydrolases
  • fumarylacetoacetase
  • Adenine