Persistent suppression of ocular neovascularization with intravitreal administration of AAVrh.10 coding for bevacizumab. Academic Article uri icon

Overview

MeSH

  • Animals
  • Bevacizumab
  • Fluorescent Antibody Technique
  • Genetic Therapy
  • Homozygote
  • Humans
  • Macaca mulatta
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Vitreous Body

MeSH Major

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Dependovirus
  • Genetic Vectors
  • Neovascularization, Pathologic
  • Retinal Pigment Epithelium
  • Vascular Endothelial Growth Factor A

abstract

  • Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of neovascular age-related macular degeneration and diabetic retinopathy. Bevacizumab, an anti-VEGF monoclonal antibody, is efficacious for these disorders, but requires monthly intravitreal administration, with associated discomfort, cost, and adverse event risk. We hypothesized that a single intravitreal administration of adeno-associated virus (AAV) vector expressing bevacizumab would result in persistent eye expression of bevacizumab and suppress VEGF-induced retinal neovascularization. We constructed an AAV rhesus serotype rh.10 vector to deliver bevacizumab (AAVrh.10BevMab) and assessed its ability to suppress neovascularization in transgenic mice overexpressing human VEGF165 in photoreceptors. Intravitreal AAVrh.10BevMab directed long-term bevacizumab expression in the retinal pigmented epithelium. Treated homozygous mice had reduced levels of neovascularization, with 90±4% reduction 168 days following treatment. Thus, a single administration of AAVrh.10BevMab provides long-term suppression of neovascularization without the costs and risks associated with the multiple administrations required for the current conventional bevacizumab monoclonal drug delivery.

publication date

  • December 2011

has subject area

  • Angiogenesis Inhibitors
  • Animals
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Dependovirus
  • Fluorescent Antibody Technique
  • Genetic Therapy
  • Genetic Vectors
  • Homozygote
  • Humans
  • Macaca mulatta
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neovascularization, Pathologic
  • Retinal Pigment Epithelium
  • Vascular Endothelial Growth Factor A
  • Vitreous Body

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3278820

Digital Object Identifier (DOI)

  • 10.1089/hum.2011.090

PubMed ID

  • 21801028

Additional Document Info

start page

  • 1525

end page

  • 1535

volume

  • 22

number

  • 12