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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.

SUBMITTER: Yin H

PROVIDER: S-EPMC4157757 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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

Yin Hao H Xue Wen W Chen Sidi S Bogorad Roman L RL Benedetti Eric E Grompe Markus M Koteliansky Victor V Sharp Phillip A PA Jacks Tyler T Anderson Daniel G DG

Nature biotechnology 20140330 6

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 ...[more]

PMID: 24681508

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