Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage

• Published in: PloS one Vol. 11; no. 3; p. e0152522
• Main Authors: Hwang, Da-Eun, Ryou, Jeong-Hyun, Oh, Jong Rok, Han, Jung Woo, Park, Tae Kwann, Kim, Hak-Sung
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.03.2016; Public Library of Science (PLoS)
• Subjects: Age; Amino Acid Sequence; Analysis; Angiogenesis; Angiogenesis Inhibitors - therapeutic use; Animals; Antibodies - chemistry; Biology and life sciences; Blindness; Cell Movement; Cell Proliferation; Choroidal Neovascularization - immunology; Diabetes mellitus; Diabetic Retinopathy - drug therapy; Diabetic Retinopathy - immunology; Engineering and Technology; Enzymes; Extracellular Signal-Regulated MAP Kinases - metabolism; Human Umbilical Vein Endothelial Cells; Humans; Immunoglobulins; Leakage; Leucine; Leucine - chemistry; Libraries; Macular degeneration; Macular Degeneration - immunology; Macular Degeneration - metabolism; Medicine and Health Sciences; Metastases; Mice; Mice, Inbred C57BL; Migration; Molecular Sequence Data; Mutation; Neoplasms - drug therapy; Neovascularization; Peptide Library; Phages; Proteins; Research and Analysis Methods; Retinopathy; Risk factors; Science; Signal Transduction; Signaling; Surface Plasmon Resonance; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - immunology; Vascularization
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0152522

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.