Adenovirus-mediated transfer of a minigene expressing multiple isoforms of VEGF is more effective at inducing angiogenesis than comparable vectors expressing individual VEGF cDNAs. Academic Article Article uri icon

Overview

MeSH

  • Alternative Splicing
  • Animals
  • Blood Vessels
  • Cells, Cultured
  • DNA, Complementary
  • Gene Expression
  • Humans
  • Leg
  • Male
  • Mice
  • Protein Isoforms
  • Rats

MeSH Major

  • Adenoviridae
  • Genetic Therapy
  • Genetic Vectors
  • Ischemia
  • Neovascularization, Physiologic
  • Vascular Endothelial Growth Factors

abstract

  • To assess the hypothesis that angiogenic gene therapy with the genomic form of vascular endothelial growth factor (VEGF) expressing the three major isoforms could be more potent than a vector expressing a single isoform, we designed an adenovirus vector (AdVEGF-All) expressing a VEGF cDNA/genomic hybrid gene. AdVEGF-All expressed all three major isoforms (121, 165, 189) in a 2:2:1 ratio. AdVEGF-All was 100-fold more potent than cDNA vectors expressing VEGF 121, 165, or 189 in restoring blood flow to the ischemic mouse hind limb. Interestingly, a mixture of Ad vectors individually expressing the VEGF 121, 165, and 189 cDNAs was equipotent to an equivalent dose of AdVEGF-All. Thus, a mixture of VEGF isoforms provides a more potent angiogenic response than a single isoform, suggesting that the individual isoforms function synergistically, an observation with important implications for gene and recombinant protein therapy.

publication date

  • January 2004

has subject area

  • Adenoviridae
  • Alternative Splicing
  • Animals
  • Blood Vessels
  • Cells, Cultured
  • DNA, Complementary
  • Gene Expression
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Ischemia
  • Leg
  • Male
  • Mice
  • Neovascularization, Physiologic
  • Protein Isoforms
  • Rats
  • Vascular Endothelial Growth Factors

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 14741779

Additional Document Info

start page

  • 67

end page

  • 75

volume

  • 9

number

  • 1