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

Mol Ther. 2004 Jan;9(1):67-75. doi: 10.1016/j.ymthe.2003.09.014.


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 types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Alternative Splicing / genetics
  • Animals
  • Blood Vessels / growth & development
  • Blood Vessels / pathology
  • Cells, Cultured
  • DNA, Complementary
  • Gene Expression
  • Genetic Therapy*
  • Genetic Vectors*
  • Humans
  • Ischemia / pathology
  • Ischemia / therapy*
  • Leg / blood supply
  • Male
  • Mice
  • Neovascularization, Physiologic*
  • Protein Isoforms / genetics
  • Rats
  • Vascular Endothelial Growth Factors / genetics*


  • DNA, Complementary
  • Protein Isoforms
  • Vascular Endothelial Growth Factors