In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is a devastating disease affecting about 1 out of 5000 male births and caused by mutations in the dystrophin gene. Genome editing has the potential to restore expression of a modified dystrophin gene from the native locus to modulate disease progression. In this stu...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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American Association for the Advancement of Science (AAAS)
2017
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| Online Access: | http://hdl.handle.net/1721.1/112732 https://orcid.org/0000-0003-2782-2509 |
| _version_ | 1811096041355739136 |
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| author | Nelson, C. E. Hakim, C. H. Ousterout, D. G. Thakore, P. I. Moreb, E. A. Rivera, R. M. C. Madhavan, S. Pan, X. Ran, F. A. Yan, W. X. Asokan, A. Duan, D. Gersbach, C. A. Zhang, Feng |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Nelson, C. E. Hakim, C. H. Ousterout, D. G. Thakore, P. I. Moreb, E. A. Rivera, R. M. C. Madhavan, S. Pan, X. Ran, F. A. Yan, W. X. Asokan, A. Duan, D. Gersbach, C. A. Zhang, Feng |
| author_sort | Nelson, C. E. |
| collection | MIT |
| description | Duchenne muscular dystrophy (DMD) is a devastating disease affecting about 1 out of 5000 male births and caused by mutations in the dystrophin gene. Genome editing has the potential to restore expression of a modified dystrophin gene from the native locus to modulate disease progression. In this study, adeno-associated virus was used to deliver the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system to the mdx mousemodel of DMD to remove the mutated exon 23 from the dystrophin gene. This includes local and systemic delivery to adult mice and systemic delivery to neonatal mice. Exon 23 deletion by CRISPR-Cas9 resulted in expression of the modified dystrophin gene, partial recovery of functional dystrophin protein in skeletal myofibers and cardiac muscle, improvement of muscle biochemistry, and significant enhancement of muscle force.This work establishes CRISPR-Cas9-based genome editing as a potential therapy to treat DMD. |
| first_indexed | 2024-09-23T16:37:24Z |
| format | Article |
| id | mit-1721.1/112732 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:37:24Z |
| publishDate | 2017 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1127322022-09-29T20:25:29Z In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy Nelson, C. E. Hakim, C. H. Ousterout, D. G. Thakore, P. I. Moreb, E. A. Rivera, R. M. C. Madhavan, S. Pan, X. Ran, F. A. Yan, W. X. Asokan, A. Duan, D. Gersbach, C. A. Zhang, Feng Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Zhang, Feng Duchenne muscular dystrophy (DMD) is a devastating disease affecting about 1 out of 5000 male births and caused by mutations in the dystrophin gene. Genome editing has the potential to restore expression of a modified dystrophin gene from the native locus to modulate disease progression. In this study, adeno-associated virus was used to deliver the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system to the mdx mousemodel of DMD to remove the mutated exon 23 from the dystrophin gene. This includes local and systemic delivery to adult mice and systemic delivery to neonatal mice. Exon 23 deletion by CRISPR-Cas9 resulted in expression of the modified dystrophin gene, partial recovery of functional dystrophin protein in skeletal myofibers and cardiac muscle, improvement of muscle biochemistry, and significant enhancement of muscle force.This work establishes CRISPR-Cas9-based genome editing as a potential therapy to treat DMD. Muscular Dystrophy Association (Award MDA277360) National Institutes of Health (U.S.) (Grant 5DP1-MH100706) National Institutes of Health (U.S.) (Grant R01DK097768) 2017-12-13T16:02:35Z 2017-12-13T16:02:35Z 2016-01 2015-09 2017-12-12T19:20:21Z Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/112732 Nelson, C. E. et al. “In Vivo Genome Editing Improves Muscle Function in a Mouse Model of Duchenne Muscular Dystrophy.” Science 351, 6271 (December 2015): 403–407 © 2016 American Association for the Advancement of Science https://orcid.org/0000-0003-2782-2509 http://dx.doi.org/10.1126/science.aad5143 Science Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Nelson, C. E. Hakim, C. H. Ousterout, D. G. Thakore, P. I. Moreb, E. A. Rivera, R. M. C. Madhavan, S. Pan, X. Ran, F. A. Yan, W. X. Asokan, A. Duan, D. Gersbach, C. A. Zhang, Feng In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy |
| title | In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy |
| title_full | In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy |
| title_fullStr | In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy |
| title_full_unstemmed | In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy |
| title_short | In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy |
| title_sort | in vivo genome editing improves muscle function in a mouse model of duchenne muscular dystrophy |
| url | http://hdl.handle.net/1721.1/112732 https://orcid.org/0000-0003-2782-2509 |
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