Genome editing abrogates angiogenesis in vivo
Author(s)Huang, Xionggao; Zhou, Guohong; Wu, Wenyi; Duan, Yajian; Ma, Gaoen; Song, Jingyuan; Xiao, Ru; Vandenberghe, Luk; Zhang, Feng; D’Amore, Patricia A.; Lei, Hetian; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Nature Publishing Group
Huang, Xionggao, et al. “Genome Editing Abrogates Angiogenesis in Vivo.” Nature Communications, vol. 8, no. 1, Dec. 2017.
Final published version