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.Abnormal angiogenesis causes many ocular diseases. Here the authors employ CRISPR/Cas9 gene editing technology to silence VEGFR2, a major regulator of angiogenesis, in retinal endothelium and abrogate angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization.

中文翻译：

---

基因组编辑消除了体内的血管生成。

血管生成在血管生成中发挥重要作用，其中血管内皮生长因子受体（VEGFR）2发挥作用，它与多种人类疾病有关，包括增生性糖尿病性视网膜病变和与湿性年龄有关的黄斑变性。在这里，我们报道了由化脓性链球菌（SpCas9）组成的腺相关病毒（AAV）介导的成簇的规则间隔的短回文重复序列（CRISPR）相关的内切核酸酶（Cas）9的系统，用于消耗血管内皮细胞（EC）中的VEGFR2。 ，其中SpCas9的表达是由细胞间粘附分子2的内皮特异性启动子驱动的。我们进一步显示，重组AAV血清型1（rAAV1）转导了病理血管的EC，并且使用rAAV1介导的CRISPR / Cas9对基因组VEGFR2基因座进行的编辑消除了氧诱导性视网膜病变和激光诱导的脉络膜新血管形成的小鼠模型中的血管生成。这项工作为基因组编辑作为治疗与血管生成相关疾病的策略奠定了坚实的基础。异常的血管生成会导致许多眼部疾病。在这里，作者采用CRISPR / Cas9基因编辑技术来沉默视网膜血管内皮中血管生成的主要调节因子VEGFR2，并消除氧诱导性视网膜病变和激光诱导的脉络膜新血管形成的小鼠模型中的血管生成。