Genome editing abrogates angiogenesis in vivo
Angiogenesis, in which vascular endothelial growth factor receptor (VEGFR) 2 plays an essential role, is associated with a variety of human diseases including proliferative diabetic retinopathy and wet age-related macular degeneration. Here we report that a system of adeno-associated virus (AAV)-med...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/112302 https://orcid.org/0000-0003-2782-2509 |
| _version_ | 1826202571593744384 |
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| author | Huang, Xionggao Zhou, Guohong Wu, Wenyi Duan, Yajian Ma, Gaoen Song, Jingyuan Xiao, Ru Vandenberghe, Luk Zhang, Feng D’Amore, Patricia A. Lei, Hetian |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Huang, Xionggao Zhou, Guohong Wu, Wenyi Duan, Yajian Ma, Gaoen Song, Jingyuan Xiao, Ru Vandenberghe, Luk Zhang, Feng D’Amore, Patricia A. Lei, Hetian |
| author_sort | Huang, Xionggao |
| collection | MIT |
| description | Angiogenesis, in which vascular endothelial growth factor receptor (VEGFR) 2 plays an essential role, is associated with a variety of human diseases including proliferative diabetic retinopathy and wet age-related macular degeneration. Here we report that a system of adeno-associated virus (AAV)-mediated clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Streptococcus pyogenes (SpCas9) is used to deplete VEGFR2 in vascular endothelial cells (ECs), whereby the expression of SpCas9 is driven by an endothelial-specific promoter of intercellular adhesion molecule 2. We further show that recombinant AAV serotyp e 1 (rAAV1) transduces ECs of pathologic vessels, and that editing of genomic VEGFR2 locus using rAAV1-mediated CRISPR/Cas9 abrogates angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization. This work establishes a strong foundation for genome editing as a strategy to treat angiogenesis-associated diseases. |
| first_indexed | 2024-09-23T12:09:38Z |
| format | Article |
| id | mit-1721.1/112302 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T12:09:38Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1123022022-10-01T08:34:39Z Genome editing abrogates angiogenesis in vivo Huang, Xionggao Zhou, Guohong Wu, Wenyi Duan, Yajian Ma, Gaoen Song, Jingyuan Xiao, Ru Vandenberghe, Luk Zhang, Feng D’Amore, Patricia A. Lei, Hetian Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Zhang, Feng Angiogenesis, in which vascular endothelial growth factor receptor (VEGFR) 2 plays an essential role, is associated with a variety of human diseases including proliferative diabetic retinopathy and wet age-related macular degeneration. Here we report that a system of adeno-associated virus (AAV)-mediated clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Streptococcus pyogenes (SpCas9) is used to deplete VEGFR2 in vascular endothelial cells (ECs), whereby the expression of SpCas9 is driven by an endothelial-specific promoter of intercellular adhesion molecule 2. We further show that recombinant AAV serotyp e 1 (rAAV1) transduces ECs of pathologic vessels, and that editing of genomic VEGFR2 locus using rAAV1-mediated CRISPR/Cas9 abrogates angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization. This work establishes a strong foundation for genome editing as a strategy to treat angiogenesis-associated diseases. National Institutes of Health (U.S.) National Eye Institute (Core Grant P30EY003790) 2017-11-28T16:12:40Z 2017-11-28T16:12:40Z 2017-07 2016-11 2017-11-21T20:31:26Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/112302 Huang, Xionggao, et al. “Genome Editing Abrogates Angiogenesis in Vivo.” Nature Communications, vol. 8, no. 1, Dec. 2017. https://orcid.org/0000-0003-2782-2509 http://dx.doi.org/10.1038/s41467-017-00140-3 Nature Communications Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Huang, Xionggao Zhou, Guohong Wu, Wenyi Duan, Yajian Ma, Gaoen Song, Jingyuan Xiao, Ru Vandenberghe, Luk Zhang, Feng D’Amore, Patricia A. Lei, Hetian Genome editing abrogates angiogenesis in vivo |
| title | Genome editing abrogates angiogenesis in vivo |
| title_full | Genome editing abrogates angiogenesis in vivo |
| title_fullStr | Genome editing abrogates angiogenesis in vivo |
| title_full_unstemmed | Genome editing abrogates angiogenesis in vivo |
| title_short | Genome editing abrogates angiogenesis in vivo |
| title_sort | genome editing abrogates angiogenesis in vivo |
| url | http://hdl.handle.net/1721.1/112302 https://orcid.org/0000-0003-2782-2509 |
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