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PMID: 24681508 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature biotechnology ·Vol. 32 ·No. 6 ·2014-06-00 ·Pages 551-3

Yin H, Xue W, Chen S, Bogorad RL, Benedetti E, Grompe M, Koteliansky V, Sharp PA, Jacks T, Anderson DG

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.

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
Chemicals
CRISPR-Associated Proteins Hydrolases fumarylacetoacetase
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Yin Hao
1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2].
Xue Wen
1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2].
Chen Sidi
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Bogorad Roman L
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Benedetti Eric
Oregon Stem Cell Center, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.
Grompe Markus
Oregon Stem Cell Center, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.
Koteliansky Victor
Skolkovo Institute of Science and Technology, Skolkovo, Russian Federation.
Sharp Phillip A
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.
Jacks Tyler
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.
Anderson Daniel G
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.
References (15)
15 references, click to expand
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Article Info
Journal
Nature biotechnology
Abbr.
Nat Biotechnol
ISSN
1546-1696
DOI
10.1038/nbt.2884
Published
2014-06-00
Epub
2014-00-30
Pages
551-3
Language
English
Region
United States
NLM ID
9604648
PMCID
PMC4157757
Subset
IM
Grants
NCI NIH HHS · P01 CA042063 · United States
NCI NIH HHS · P30 CA014051 · United States
NCI NIH HHS · P30-CA14051 · United States
NCI NIH HHS · 5-U54-CA151884-04 · United States
NCI NIH HHS · 2-PO1-CA42063 · United States
NCI NIH HHS · R01-CA133404 · United States
NCI NIH HHS · U54 CA151884 · United States
NCI NIH HHS · R01 CA133404 · United States
Howard Hughes Medical Institute · United States
NCI NIH HHS · K99 CA169512 · United States
NCI NIH HHS · R00 CA169512 · United States
NCI NIH HHS · 1K99CA169512 · United States
NIDDK NIH HHS · R01 DK048252 · United States
Corrections
ErratumIn
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CommentIn
PMID: 24804755
External Links
PubMed source DOI: 10.1038/nbt.2884 PMC Full Text View journal details
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