Intratracheal adenovirus-mediated gene transfer is optimal in experimental lung transplantation

Objective: Gene transfer to experimental lung grafts has been shown to reduce ischemia-reperfusion injury and acute rejection. The optimal delivery route should produce high lung expression with no inflammation and minimal systemic expression. The goal of this study was to determine the optimal gene transfer route for use in experimental lung transplantation. Methods: F344 rats were injected with 2.9 x 10(10) plaque-forming units of adenovirus vector encoding beta-galactosidase through intratracheal, intravenous, intraperitoneal, or intramuscular delivery routes and killed 48 hours later. Gene expression was measured by means of enzyme-linked immunosorbent assay. Results: Intratracheal delivery produces significantly greater gene expression in the lung (75,350 +/- 47,288 pg/100 mug of protein, P < .001 vs intravenous, intraperitoneal, and intramuscular routes) and minimal systemic expression (nonsignificant in serum, kidney, liver, spleen, and muscle vs that seen in control animals, P = .016 for heart). Immunohistochemistry staining showed beta-galactosidase expression in the bronchial epithelium of lungs transfected through the intratracheal route with mild inflammation. Conclusions: Intratracheal gene transfer provides significant expression in the lung with mild to no inflammation and minimal systemic expression. This delivery strategy has tremendous potential in experimental lung transplant models to reduce ischemia-reperfusion injury and acute allograft rejection and should be investigated further.