Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype
- PMID: 24681508
- PMCID: PMC4157757
- DOI: 10.1038/nbt.2884
Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype
Erratum in
- Nat Biotechnol. 2014 Sep;32(9):952
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.
Figures
Comment in
-
CRISPR technology for gene therapy.Nat Med. 2014 May;20(5):476-7. doi: 10.1038/nm.3566. Nat Med. 2014. PMID: 24804755 No abstract available.
Similar articles
-
Cas9-nickase-mediated genome editing corrects hereditary tyrosinemia in rats.J Biol Chem. 2018 May 4;293(18):6883-6892. doi: 10.1074/jbc.RA117.000347. Epub 2018 Mar 5. J Biol Chem. 2018. PMID: 29507093 Free PMC article.
-
Curative Ex Vivo Hepatocyte-Directed Gene Editing in a Mouse Model of Hereditary Tyrosinemia Type 1.Hum Gene Ther. 2018 Nov;29(11):1315-1326. doi: 10.1089/hum.2017.252. Epub 2018 Jun 22. Hum Gene Ther. 2018. PMID: 29764210 Free PMC article.
-
Reprogramming metabolic pathways in vivo with CRISPR/Cas9 genome editing to treat hereditary tyrosinaemia.Nat Commun. 2016 Aug 30;7:12642. doi: 10.1038/ncomms12642. Nat Commun. 2016. PMID: 27572891 Free PMC article.
-
CRISPR/Cas9 system: a powerful technology for in vivo and ex vivo gene therapy.Sci China Life Sci. 2017 May;60(5):468-475. doi: 10.1007/s11427-017-9057-2. Epub 2017 Apr 20. Sci China Life Sci. 2017. PMID: 28534255 Review.
-
The application of genome editing in studying hearing loss.Hear Res. 2015 Sep;327:102-8. doi: 10.1016/j.heares.2015.04.016. Epub 2015 May 15. Hear Res. 2015. PMID: 25987504 Free PMC article. Review.
Cited by 322 articles
-
CRISPR/Cas9-related technologies in liver diseases: from feasibility to future diversity.Int J Biol Sci. 2020 Jun 1;16(13):2283-2295. doi: 10.7150/ijbs.33481. eCollection 2020. Int J Biol Sci. 2020. PMID: 32760197 Free PMC article. Review.
-
Protein Degradation and the Pathologic Basis of Phenylketonuria and Hereditary Tyrosinemia.Int J Mol Sci. 2020 Jul 15;21(14):4996. doi: 10.3390/ijms21144996. Int J Mol Sci. 2020. PMID: 32679806 Free PMC article. Review.
-
Modelling Epithelial Ovarian Cancer in Mice: Classical and Emerging Approaches.Int J Mol Sci. 2020 Jul 7;21(13):4806. doi: 10.3390/ijms21134806. Int J Mol Sci. 2020. PMID: 32645943 Free PMC article. Review.
-
Lipid nanoparticle technology for therapeutic gene regulation in the liver.Adv Drug Deliv Rev. 2020 Jul 2:S0169-409X(20)30072-7. doi: 10.1016/j.addr.2020.06.026. Online ahead of print. Adv Drug Deliv Rev. 2020. PMID: 32622021 Free PMC article. Review.
-
Systemic nanoparticle delivery of CRISPR-Cas9 ribonucleoproteins for effective tissue specific genome editing.Nat Commun. 2020 Jun 26;11(1):3232. doi: 10.1038/s41467-020-17029-3. Nat Commun. 2020. PMID: 32591530 Free PMC article.
Publication types
MeSH terms
Substances
Grant support
- R01-CA133404/CA/NCI NIH HHS/United States
- U54 CA151884/CA/NCI NIH HHS/United States
- P01 CA042063/CA/NCI NIH HHS/United States
- P30 CA014051/CA/NCI NIH HHS/United States
- P30-CA14051/CA/NCI NIH HHS/United States
- 5-U54-CA151884-04/CA/NCI NIH HHS/United States
- R01 CA133404/CA/NCI NIH HHS/United States
- Howard Hughes Medical Institute/United States
- 2-PO1-CA42063/CA/NCI NIH HHS/United States
- K99 CA169512/CA/NCI NIH HHS/United States
- R00 CA169512/CA/NCI NIH HHS/United States
- 1K99CA169512/CA/NCI NIH HHS/United States
- R01 DK048252/DK/NIDDK NIH HHS/United States
LinkOut - more resources
-
Full Text Sources
-
Other Literature Sources
-
Medical
-
Molecular Biology Databases
-
Research Materials
-
Miscellaneous