Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype

Nat Biotechnol. 2014 Jun;32(6):551-3. doi: 10.1038/nbt.2884. Epub 2014 Mar 30.


We demonstrate CRISPR-Cas9-mediated correction of a Fah mutation in hepatocytes in a mouse model of the human disease hereditary tyrosinemia. Delivery of components of the CRISPR-Cas9 system by hydrodynamic injection resulted in initial expression of the wild-type Fah protein in ∼1/250 liver cells. Expansion of Fah-positive hepatocytes rescued the body weight loss phenotype. Our study indicates that CRISPR-Cas9-mediated genome editing is possible in adult animals and has potential for correction of human genetic diseases.

Publication types

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

MeSH terms

  • Animals
  • CRISPR-Associated Proteins / genetics*
  • CRISPR-Cas Systems*
  • Gene Editing / methods*
  • Genetic Therapy / methods*
  • Genome / genetics
  • Hydrolases / genetics*
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Phenotype
  • Treatment Outcome
  • Tyrosinemias / therapy*


  • CRISPR-Associated Proteins
  • Hydrolases
  • fumarylacetoacetase