title: Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype.
abstract: 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.
authors.affiliation: 1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2].
authors.forename: Hao
authors.initials: H
authors.lastname: Yin
authors.affiliation: 1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2].
authors.forename: Wen
authors.initials: W
authors.lastname: Xue
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Sidi
authors.initials: S
authors.lastname: Chen
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Roman L
authors.initials: RL
authors.lastname: Bogorad
authors.affiliation: Oregon Stem Cell Center, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Benedetti
authors.affiliation: Oregon Stem Cell Center, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Grompe
authors.affiliation: Skolkovo Institute of Science and Technology, Skolkovo, Russian Federation.
authors.forename: Victor
authors.initials: V
authors.lastname: Koteliansky
authors.affiliation: 1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Sharp
authors.affiliation: 1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
authors.affiliation: 1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Harvard-MIT Division of Health Sciences & Technology, Cambridge, Massachusetts, USA. [4] Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D000818:Animals; D064130:CRISPR-Associated Proteins / Q000235:genetics*; D064113:CRISPR-Cas Systems; D000072669:Gene Editing / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D016678:Genome / Q000235:genetics; D006867:Hydrolases / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D016896:Treatment Outcome; D020176:Tyrosinemias / Q000628:therapy*
chemical_list: D064130:CRISPR-Associated Proteins; D006867:Hydrolases; C020156:fumarylacetoacetase