| Title |
Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications
|
|---|---|
| Published in |
Angiogenesis, September 2012
|
| DOI | 10.1007/s10456-012-9302-0 |
| Pubmed ID | |
| Authors |
Andreas Stahl, Michael T. Stumpp, Anja Schlegel, Savira Ekawardhani, Christina Lehrling, Gottfried Martin, Maya Gulotti-Georgieva, Denis Villemagne, Patrik Forrer, Hansjürgen T. Agostini, H. Kaspar Binz |
| 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. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 101 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | <1% |
| Germany | 1 | <1% |
| Switzerland | 1 | <1% |
| Unknown | 98 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 23 | 23% |
| Student > Ph. D. Student | 22 | 22% |
| Student > Master | 12 | 12% |
| Other | 11 | 11% |
| Student > Bachelor | 7 | 7% |
| Other | 12 | 12% |
| Unknown | 14 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 27 | 27% |
| Biochemistry, Genetics and Molecular Biology | 22 | 22% |
| Medicine and Dentistry | 11 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 8 | 8% |
| Engineering | 6 | 6% |
| Other | 10 | 10% |
| Unknown | 17 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 June 2022.
All research outputs
#3,183,067
of 22,721,584 outputs
Outputs from Angiogenesis
#50
of 536 outputs
Outputs of similar age
#22,670
of 168,727 outputs
Outputs of similar age from Angiogenesis
#3
of 20 outputs
Altmetric has tracked 22,721,584 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 536 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.1. This one has done particularly well, scoring higher than 90% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 168,727 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 20 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.