Abstract
Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness among people over the age of 60. Vascular endothelial growth factor (VEGF) plays a major role in pathological angiogenesis in AMD. Herein, we present the development of an anti- human VEGF repebody, which is a small-sized protein binder consisting of leucine-rich repeat (LRR) modules. The anti-VEGF repebody selected through a phage-display was shown to have a high affinity and specificity for human VEGF. We demonstrate that this repebody effectively inhibits in vitro angiogenic cellular processes, such as proliferation and migration, by blocking the VEGF-mediated signaling pathway. The repebody was also shown to have a strong suppression effect on choroidal neovascularization (CNV) and vascular leakage in vivo. Our results indicate that the anti-VEGF repebody has a therapeutic potential for treating neovascular AMD as well as other VEGF-involved diseases including diabetic retinopathy and metastatic cancers.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Angiogenesis Inhibitors / therapeutic use
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Animals
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Antibodies / chemistry*
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Cell Movement
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Cell Proliferation
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Choroidal Neovascularization / immunology*
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Diabetic Retinopathy / drug therapy
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Diabetic Retinopathy / immunology
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Human Umbilical Vein Endothelial Cells
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Humans
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Leucine / chemistry*
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Macular Degeneration / immunology
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Macular Degeneration / metabolism
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Mutation
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Neoplasms / drug therapy
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Peptide Library
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Signal Transduction
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Surface Plasmon Resonance
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Vascular Endothelial Growth Factor A / immunology*
Substances
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Angiogenesis Inhibitors
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Antibodies
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Peptide Library
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Extracellular Signal-Regulated MAP Kinases
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Leucine
Grants and funding
This research was supported by the Mid-career Researcher Program (NRF-2014R1A2A1A01004198) and Global Research Laboratory (NRF-2015K1A1A2033346) of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning, and Brain Korea 21 funded by the Ministry of Education.