ArticleAngiogenesis2013
Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications.
Article in Angiogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 69 citations in OpenAlex.
- Synonymous Codons and Hydrophobicity Optimization of Post-translational Signal Peptide PelB Increase Phage Display Efficiency of DARPins.ACS synthetic biology · 2022Article
- Cytosolic Delivery of Small Protein Scaffolds Enables Efficient Inhibition of Ras and Myc.Molecular pharmaceutics · 2022Article
- A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics.Molecules (Basel, Switzerland) · 2021Review
- Extending traditional antibody therapies: Novel discoveries in immunotherapy and clinical applications.Molecular therapy oncolytics · 2021Review
- Neovascular Age-Related Macular Degeneration: Therapeutic Management and New-Upcoming Approaches.International journal of molecular sciences · 2020Review
- Implantable anti-angiogenic scaffolds for treatment of neovascular ocular pathologies.Drug delivery and translational research · 2020Review
- DARPin Ec1-LMWP protein scaffold in targeted delivery of siRNA molecules through EpCAM cancer stem cell marker.Molecular biology reports · 2020Article
- Soluble ligands as drug targets.Nature reviews. Drug discovery · 2020Review
- Beyond Antibodies: The DARPinBioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020Review
- AAV2/8 Anti-angiogenic Gene Therapy Using Single-Chain Antibodies Inhibits Murine Choroidal Neovascularization.Molecular therapy. Methods & clinical development · 2019Article
- Review
- Sensing and responding to allergic response cytokines through a genetically encoded circuit.Nature communications · 2017Article
- Review
- Alternative reagents to antibodies in imaging applications.Biophysical reviews · 2017Review
- Exploring the cross talk between ER stress and inflammation in age-related macular degeneration.PloS one · 2017Article
- Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage.PloS one · 2016Article
- Protein interference applications in cellular and developmental biology using DARPins that recognize GFP and mCherry.Biology open · 2014Article
- Antagonism of PDGF-BB suppresses subretinal neovascularization and enhances the effects of blocking VEGF-A.Angiogenesis · 2014Article
- Recent developments in the treatment of age-related macular degeneration.The Journal of clinical investigation · 2014Review
- Do nutritional supplements have a role in age macular degeneration prevention?Journal of ophthalmology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The next-generation ophthalmic anti-VEGF therapeutics must aim at being superior to the currently available agents with regard to potency and improved drug delivery, while still being stable and safe to use at elevated concentrations. We show here the generation of a set of highly potent VEGF-A antagonistic DARPins (designed ankyrin repeat proteins) delivering these properties. DARPins with single-digit picomolar affinity to human VEGF-A were generated using ribosome display selections. Specific and potent human VEGF-A binding was confirmed by ELISA and endothelial cell sprouting assays. Cross-reactivity with VEGF-A of several species was confirmed by ELISA. Intravitreally injected DARPin penetrated into the retina and reduced fluorescein extravasation in a rabbit model of vascular leakage. In addition, topical DARPin application was found to diminish corneal neovascularization in a rabbit suture model, and to suppress laser-induced neovascularization in a rat model. Even at elevated doses, DARPins were safe to use. The fact that several DARPins are highly active in various assays illustrates the favorable class behavior of the selected binders. Anti-VEGF-A DARPins thus represent a novel class of highly potent and specific drug candidates for the treatment of neovascular eye diseases in both the posterior and the anterior eye chamber.
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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.