Dose-dependent neovascularization-promoting effect of adenovirus vector CI-1023 in a rat hindlimb ischaemic model

CI-1023 (Ad_GVVEGF121.10) is a replication-deficient adenovirus vector (complete Ela^-, partial Elb^-, partial E3 ^-) delivering human vascular endothelial growth factor-121 gene. Previous studies from this group have established that CI-1023 can successfully transfer human vascular endothelial growth factor-121 gene resulting in local tissue expression of vascular endothelial growth factor protein. The purpose of this study was to evaluate neovascularization-promoting potency and efficacy of CI-1023 in a wide dose range. In a rat hindlimb ischaemic model, we measured neovascularization-promoting effect of CI-1023 using three end-points: post mortem angiography, immuno-histochemisty and Laser Doppler scanning of tissue blood perfusion. Neovascularization-promoting activity of CI-1023 over the dose range of 4×10⁶ pu-4×10¹⁰ pu was evaluated. Our data demonstrated an obvious dose-dependent effect between 4×10 ⁶ pu-4×10⁸ pu. The neovascularizing effect is somewhat plateaued at the levels between 4×10⁸ pu and 4×10¹⁰ pu. We conclude CI-1023 is a potent neovascularization- promoting compound, with a dose-dependent effect between 4×10⁶ pu-4×10⁸ pu in the rat hindlimb ischaemic model.