ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Dual suppression of hemangiogenesis and lymphangiogenesis by splice-shifting morpholinos targeting vascular endothelial growth factor receptor 2 (KDR).
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Therapeutic Targeting of RNA Splicing in Cancer.Genes · 2023Review
- Targeted splicing therapy: new strategies for colorectal cancer.Frontiers in oncology · 2023Review
- Biomaterials for Modulating Lymphatic Function in Immunoengineering.ACS pharmacology & translational science · 2019Review
- Effect of Anti-C5a Therapy in a Murine Model of Early/Intermediate Dry Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2018Article
- RBPs Play Important Roles in Vascular Endothelial Dysfunction Under Diabetic Conditions.Frontiers in physiology · 2018Review
- Targeted Delivery of FLT-Morpholino Using Cyclic RGD Peptide.Translational vision science & technology · 2017Article
- Effect of itraconazole on the cornea in a murine suture model and penetrating keratoplasty model.International journal of ophthalmology · 2017Article
- Effect of sorafenib in a murine high risk penetrating keratoplasty model.International journal of ophthalmology · 2017Article
- Splice-switching antisense oligonucleotides as therapeutic drugs.Nucleic acids research · 2016Review
- Subretinal AAV2.COMP-Ang1 suppresses choroidal neovascularization and vascular endothelial growth factor in a murine model of age-related macular degeneration.Experimental eye research · 2016Article
- Effect of trapping vascular endothelial growth factor-A in a murine model of dry eye with inflammatory neovascularization.International journal of ophthalmology · 2016Article
- Article
- Development of therapeutic splice-switching oligonucleotides.Human gene therapy · 2014Review
- Lymphangiogenic factors, mechanisms, and applications.The Journal of clinical investigation · 2014Review
- Is fibroblast growth factor receptor 4 a suitable target of cancer therapy?Current pharmaceutical design · 2014Review
- mPEG-PAMAM-G4 nucleic acid nanocomplexes: enhanced stability, RNase protection, and activity of splice switching oligomer and poly I:C RNA.Biomacromolecules · 2013Article
- Antisense Modulation of RNA Processing as a Therapeutic Approach in Cancer Therapy.Drug discovery today. Therapeutic strategies · 2013Article
- Vascular Endothelial Growth Factor Receptor 1 morpholino increases graft survival in a murine penetrating keratoplasty model.Investigative ophthalmology & visual science · 2012Article
- Gene therapy in corneal transplantation.Seminars in ophthalmologyReview
- Targeting RNA splicing for disease therapy.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The KDR gene, which participates in angiogenesis and lymphangiogenesis, produces two functionally distinct protein products, membrane-bound KDR (mbKDR) and its isoform, soluble KDR (sKDR). Since sKDR does not have a tyrosine kinase domain and does not dimerize, it is principally an antagonist of lymphangiogenesis by sequestering VEGF-C. Alternative polyadenylation of exon 30 or intron 13 leads to the production of mbKDR or sKDR, respectively, yet the regulatory mechanisms are unknown. Here we show that an antisense morpholino oligomer directed against the exon 13-intron 13 junction increases sKDR (suppressing lymphangiogenesis) and decreases mbKDR (inhibiting hemangiogenesis). The latent polyadenylation site in intron 13 of KDR is activated by blocking the upstream 5' splicing site with an antisense morpholino oligomer. Intravitreal morpholino injection suppressed laser choroidal neovascularization while increasing sKDR. In the mouse cornea, subconjunctival injection of the morpholino-inhibited corneal angiogenesis and lymphangiogenesis, and suppressed graft rejection after transplantation. Thus, this morpholino can be used for concurrent suppression of hemangiogenesis and lymphangiogenesis. This study offers new insight into the mechanisms and potential therapeutic modulation of alternative polyadenylation.
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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.