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

• Main Authors: Yin, Hao (Contributor), Xue, Wen (Contributor), Chen, Sidi (Contributor), Benedetti, Eric (Author), Grompe, Markus (Author), Kotelianski, Victor E. (Author), Bogorad, Roman (Contributor), Sharp, Phillip A. (Contributor), Anderson, Daniel Griffith (Contributor), Jacks, Tyler E (Author)
• Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science (Contributor), Harvard University- (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor), Jacks, Tyler E. (Contributor)
• Format: Article
• Language: English
• Published: Nature Publishing Group, 2015-06-05T17:19:53Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Cancer Institute (U.S.) (Grant 2-PO1-CA42063)
National Cancer Institute (U.S.) (Core Grant P30-CA14051)
National Institutes of Health (U.S.) (Grant R01-CA133404)
David H. Koch Institute for Integrative Cancer Research at MIT (Marie D. and Pierre Casimir-Lambert Fund)
National Institutes of Health (U.S.) (Centers for Cancer Nanotechnology Excellence 5-U54-CA151884-04)
MIT-Harvard Center of Cancer Nanotechnology Excellence
National Institutes of Health (U.S.) (1K99CA169512)