ObjectiveThe purpose of this study was to investigate the effect of recombinant adeno-associated viral (rAAV) vector-mediated human vascular endothelial growth factor (VEGF165) transfer on experimental burn wounds.DesignRandomized experiment.SettingResearch laboratory.SubjectsC57BL/6 male mice weighing 25–30 g.InterventionsMice were immersed in 80°C water for 10 secs to achieve a partial-thickness scald burn. Animals were randomized to receive at two injection sites on the edge of the burn either 1011copies of the rAAV-VEGF165 or the vector carrying the control and inert gene &bgr;-galactosidase (rAAV-LacZ). On day 14 the animals were killed. Burn areas were used for histologic examination, evaluation of VEGF expression (immunohistochemistry) and VEGF wound content (enzyme-linked immunosorbent assay), determination of wound nitrite, and measurement of messenger RNA (mRNA) for endothelial and inducible nitric oxide synthase (eNOS and iNOS).Measurements and Main ResultsrAAV-VEGF165 increased epithelial proliferation, angiogenesis, and maturation of the extracellular matrix. Furthermore, gene transfer enhanced VEGF expression, studied by immunohistochemistry, and the wound content of the mature protein (rAAV-LacZ, 11 ± 5 pg/wound; rAAV-VEGF165, 104 ± 7 pg/wound). Moreover, VEGF165 gene transfer increased wound content of nitrate. Finally, rAAV-VEGF165 administration enhanced the messenger RNA for eNOS (rAAV-VEGF165, 1.1 ± 0.2 relative amount of eNOS mRNA; rAAV-LacZ, 0.66 ± 0.3 relative amount of eNOS mRNA) and iNOS (rAAV-VEGF165, 0.8 ± 0.09 relative amount of iNOS mRNA; rAAV-LacZ, 0.45 ± 0.05 relative amount of iNOS mRNA).ConclusionOur study suggests that rAAV-VEGF gene transfer may be an effective therapeutic approach to improve clinical outcomes after thermal injury.