ArticleInvestigative ophthalmology & visual science2017
AAV-CRISPR/Cas9-Mediated Depletion of VEGFR2 Blocks Angiogenesis In Vitro.
Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- AviTag-seq unifies nucleotide-resolution maps of CRISPR off-targets and AAV vector integrations.Communications biology · 2026Article
- Gene therapy in neovascular age related macular degeneration: an update.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Review
- Gene Therapy in Diabetic Retinopathy and Diabetic Macular Edema: An Update.Journal of clinical medicine · 2025Review
- CYTOR-NFAT1 feedback loop regulates epithelial-mesenchymal transition of retinal pigment epithelial cells.Human cell · 2024Article
- Multifunctional nano-in-micro delivery systems for targeted therapy in fundus neovascularization diseases.Journal of nanobiotechnology · 2024Review
- Genetic and functional correction of argininosuccinate lyase deficiency using CRISPR adenine base editors.American journal of human genetics · 2024Article
- Systemic Cytokines in Retinopathy of Prematurity.Journal of personalized medicine · 2023Review
- Genome Editing Inhibits Retinal Angiogenesis in a Mouse Model of Oxygen-Induced Retinopathy.Methods in molecular biology (Clifton, N.J.) · 2023Article
- HIF1A Knockout by Biallelic and Selection-Free CRISPR Gene Editing in Human Primary Endothelial Cells with Ribonucleoprotein Complexes.Biomolecules · 2022Article
- New Aspects on the Treatment of Retinopathy of Prematurity: Currently Available Therapies and Emerging Novel Therapeutics.International journal of molecular sciences · 2022Review
- CRISPR/Cas systems: Delivery and application in gene therapy.Frontiers in bioengineering and biotechnology · 2022Review
- Nanotechnology for Age-Related Macular Degeneration.Pharmaceutics · 2021Review
- CRISPR-Based Genome Editing as a New Therapeutic Tool in Retinal Diseases.Molecular biotechnology · 2021Review
- Angiogenesis: A Cellular Response to Traumatic Injury.Shock (Augusta, Ga.) · 2021Review
- Axl Is Essential forFrontiers in medicine · 2021Article
- Circular Ribonucleic Acid circFTO Promotes Angiogenesis and Impairs Blood-Retinal BarrierFrontiers in molecular biosciences · 2021Article
- Gene Therapy Intervention in Neovascular Eye Disease: A Recent Update.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- The Role of Inflammation in Age-Related Macular Degeneration.International journal of biological sciences · 2020Review
- CRISPR Technology for Ocular Angiogenesis.Frontiers in genome editing · 2020Review
- Precise CCM1 gene correction and inactivation in patient-derived endothelial cells: Modeling Knudson's two-hit hypothesis in vitro.Molecular genetics & genomic medicine · 2019Article
Corrections and comments
- Erratum issuedErratum.2017
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Purpose: Pathologic angiogenesis is a component of many diseases, including neovascular age-related macular degeneration, proliferation diabetic retinopathy, as well as tumor growth and metastasis. The purpose of this project was to examine whether the system of adeno-associated viral (AAV)-mediated CRISPR (clustered regularly interspaced short palindromic repeats)-associated endonuclease (Cas)9 can be used to deplete expression of VEGF receptor 2 (VEGFR2) in human vascular endothelial cells in vitro and thus suppress its downstream signaling events. Methods: The dual AAV system of CRISPR/Cas9 from Streptococcus pyogenes (AAV-SpGuide and -SpCas9) was adapted to edit genomic VEGFR2 in primary human retinal microvascular endothelial cells (HRECs). In this system, the endothelial-specific promoter for intercellular adhesion molecule 2 (ICAM2) was cloned into the dual AAV vectors of SpGuide and SpCas9 for driving expression of green fluorescence protein (GFP) and SpCas9, respectively. These two AAV vectors were applied to production of recombinant AAV serotype 5 (rAAV5), which were used to infect HRECs for depletion of VEGFR2. Protein expression was determined by Western blot; and cell proliferation, migration, as well as tube formation were examined. Results: AAV5 effectively infected vascular endothelial cells (ECs) and retinal pigment epithelial (RPE) cells; the ICAM2 promoter drove expression of GFP and SpCas9 in HRECs, but not in RPE cells. The results showed that the rAAV5-CRISPR/Cas9 depleted VEGFR2 by 80% and completely blocked VEGF-induced activation of Akt, and proliferation, migration as well as tube formation of HRECs. Conclusions: AAV-CRISRP/Cas9-mediated depletion of VEGFR2 is a potential therapeutic strategy for pathologic angiogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.