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Genome editing abrogates angiogenesis in vivo

Author

Listed:
  • Xionggao Huang

    (Harvard Medical School
    Harvard Medical School
    Hainan Eye Hospital)

  • Guohong Zhou

    (Harvard Medical School
    Harvard Medical School
    Shanxi Eye Hospital)

  • Wenyi Wu

    (Harvard Medical School
    Harvard Medical School
    Department of Ophthalmology, Second Xiangya Hospital, Second Xiangya Hospital, Central South University)

  • Yajian Duan

    (Harvard Medical School
    Harvard Medical School
    Shanxi Eye Hospital)

  • Gaoen Ma

    (Harvard Medical School
    Harvard Medical School)

  • Jingyuan Song

    (Harvard Medical School
    Harvard Medical School
    Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Ru Xiao

    (Harvard Medical School
    Harvard Medical School)

  • Luk Vandenberghe

    (Harvard Medical School
    Harvard Medical School)

  • Feng Zhang

    (Broad Institute of the Massachusetts Institute of Technology and Harvard University)

  • Patricia A. D’Amore

    (Harvard Medical School
    Harvard Medical School)

  • Hetian Lei

    (Harvard Medical School
    Harvard Medical School)

Abstract

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 serotype 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.

Suggested Citation

  • Xionggao Huang & Guohong Zhou & Wenyi Wu & Yajian Duan & Gaoen Ma & Jingyuan Song & Ru Xiao & Luk Vandenberghe & Feng Zhang & Patricia A. D’Amore & Hetian Lei, 2017. "Genome editing abrogates angiogenesis in vivo," Nature Communications, Nature, vol. 8(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00140-3
    DOI: 10.1038/s41467-017-00140-3
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    Cited by:

    1. Lulu Xue & Alex G. Hamilton & Gan Zhao & Zebin Xiao & Rakan El-Mayta & Xuexiang Han & Ningqiang Gong & Xinhong Xiong & Junchao Xu & Christian G. Figueroa-Espada & Sarah J. Shepherd & Alvin J. Mukalel , 2024. "High-throughput barcoding of nanoparticles identifies cationic, degradable lipid-like materials for mRNA delivery to the lungs in female preclinical models," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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