title: Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage.
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.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.
authors.forename: Da-Eun
authors.initials: DE
authors.lastname: Hwang
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.|Graduate School of Medical Science & Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Ryou
authors.affiliation: Department of Ophthalmology, Soonchunhyang University, College of Medicine, Bucheon Hospital, Bucheon, Korea.
authors.forename: Jong Rok
authors.initials: JR
authors.lastname: Oh
authors.affiliation: Department of Ophthalmology, Soonchunhyang University, College of Medicine, Bucheon Hospital, Bucheon, Korea.
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Han
authors.affiliation: Department of Ophthalmology, Soonchunhyang University, College of Medicine, Bucheon Hospital, Bucheon, Korea.
authors.forename: Tae Kwann
authors.initials: TK
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.
authors.forename: Hak-Sung
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D002465:Cell Movement; D049109:Cell Proliferation; D020256:Choroidal Neovascularization / Q000276:immunology*; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007930:Leucine / Q000737:chemistry*; D008268:Macular Degeneration / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy; D019151:Peptide Library; D015398:Signal Transduction; D020349:Surface Plasmon Resonance; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
chemical_list: D020533:Angiogenesis Inhibitors; D000906:Antibodies; D019151:Peptide Library; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D048049:Extracellular Signal-Regulated MAP Kinases; D007930:Leucine