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 uri icon

Overview

MeSH Major

  • Chromosome Aberrations
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 8
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Translocation, Genetic

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

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1016/j.ymthe.2003.09.014

Additional Document Info

start page

  • 67

end page

  • 75

volume

  • 9

number

  • 1