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

Hao Yin; Wen Xue; Sidi Chen; Roman L. Bogorad; Eric Benedetti; Markus Grompe; Victor Koteliansky; Phillip A. Sharp; Tyler Jacks; Daniel G. Anderson

doi:10.1038/nbt.2884

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

Hao Yin, Wen Xue, Sidi Chen, Roman L. Bogorad, Eric Benedetti, Markus Grompe, Victor Koteliansky, Phillip A. Sharp, Tyler Jacks, Daniel G. Anderson

Research output: Contribution to journal › Article › peer-review

770 Scopus citations

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 ~1/41/250 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.

Original language	English (US)
Pages (from-to)	551-553
Number of pages	3
Journal	Nature biotechnology
Volume	32
Issue number	6
DOIs	https://doi.org/10.1038/nbt.2884
State	Published - Jun 2014

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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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 ~1/41/250 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.",

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AU - Yin, Hao

AU - Xue, Wen

AU - Chen, Sidi

AU - Bogorad, Roman L.

AU - Benedetti, Eric

AU - Grompe, Markus

AU - Koteliansky, Victor

AU - Sharp, Phillip A.

AU - Jacks, Tyler

AU - Anderson, Daniel G.

PY - 2014/6

Y1 - 2014/6

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AB - 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 ~1/41/250 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.

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

Abstract

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