Adenovirus-mediated transfer of a minigene expressing multiple isoforms of VEGF is more effective at inducing angiogenesis than comparable vectors expressing individual VEGF cDNAs.
| Publication Type | Academic Article |
| Authors | Whitlock P, Hackett N, Leopold P, Rosengart T, Crystal R |
| Journal | Mol Ther |
| Volume | 9 |
| Issue | 1 |
| Pagination | 67-75 |
| Date Published | 01/01/2004 |
| ISSN | 1525-0016 |
| Keywords | 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. |
| DOI | 10.1016/j.ymthe.2003.09.014 |
| PubMed ID | 14741779 |