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

Paul R. Whitlock, Neil R. Hackett, Philip L. Leopold, Todd K. Rosengart, Ronald Crystal

Research output: Contribution to journalArticle

41 Citations (Scopus)

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-AII) expressing a VEGF cDNA/genomic hybrid gene. AdVEGF-AII expressed all three major isoforms (121, 165, 189) in a 2:2:1 ratio. AdVEGF-AII 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-AII. 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.

Original languageEnglish
Pages (from-to)67-75
Number of pages9
JournalMolecular Therapy
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Jan 2004
Externally publishedYes

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Keywords

  • Angiogenesis
  • Endothelium
  • Gene therapy
  • Vascular disease
  • VEGF

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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