Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype
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....
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2015
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| Online Access: | http://hdl.handle.net/1721.1/97197 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-6898-3793 |
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| author | Yin, Hao Xue, Wen Chen, Sidi Benedetti, Eric Grompe, Markus Kotelianski, Victor E. Bogorad, Roman Sharp, Phillip A. Anderson, Daniel Griffith Jacks, Tyler E |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Yin, Hao Xue, Wen Chen, Sidi Benedetti, Eric Grompe, Markus Kotelianski, Victor E. Bogorad, Roman Sharp, Phillip A. Anderson, Daniel Griffith Jacks, Tyler E |
| author_sort | Yin, Hao |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:12:30Z |
| format | Article |
| id | mit-1721.1/97197 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:12:30Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/971972022-09-30T08:16:39Z Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype Yin, Hao Xue, Wen Chen, Sidi Benedetti, Eric Grompe, Markus Kotelianski, Victor E. Bogorad, Roman Sharp, Phillip A. Anderson, Daniel Griffith Jacks, Tyler E Massachusetts Institute of Technology. Institute for Medical Engineering & Science Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Yin, Hao Xue, Wen Chen, Sidi Bogorad, Roman Sharp, Phillip A. Jacks, Tyler E. Anderson, Daniel Griffith 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) 2015-06-05T17:19:53Z 2015-06-05T17:19:53Z 2014-03 2013-12 Article http://purl.org/eprint/type/JournalArticle 1087-0156 1546-1696 http://hdl.handle.net/1721.1/97197 Yin, Hao, Wen Xue, Sidi Chen, Roman L Bogorad, Eric Benedetti, Markus Grompe, Victor Koteliansky, Phillip A Sharp, Tyler Jacks, and Daniel G Anderson. “Genome Editing with Cas9 in Adult Mice Corrects a Disease Mutation and Phenotype.” Nature Biotechnology 32, no. 6 (March 30, 2014): 551–553. https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-6898-3793 en_US http://dx.doi.org/10.1038/nbt.2884 Nature Biotechnology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Yin, Hao Xue, Wen Chen, Sidi Benedetti, Eric Grompe, Markus Kotelianski, Victor E. Bogorad, Roman Sharp, Phillip A. Anderson, Daniel Griffith Jacks, Tyler E Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype |
| title | Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype |
| title_full | Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype |
| title_fullStr | Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype |
| title_full_unstemmed | Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype |
| title_short | Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype |
| title_sort | genome editing with cas9 in adult mice corrects a disease mutation and phenotype |
| url | http://hdl.handle.net/1721.1/97197 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-6898-3793 |
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