Enhancement of adenoviral transduction with polycationic liposomes in vivo

Although the high transfection efficiency with adenovirus in vitro is well documented, it is still not clear whether adenoviral vectors are effective in vivo in solid tumor models. in our preliminary experiment, transduction of tumor tissue was limited to just around the injection site after intratu moral injection of the adenoviral vector. To improve the transduction effic iency in vivo, we tried a combination of adenoviral vector and liposome in our animal model. Adenovirus carrying human placental alkaline phosphatase (AdALP) and Lipofectamine or 1,3-di-oleoyloxy-2-(6-carboxyspermyl)-propylam ide were used as a marker gene and the cationic liposome, respectively. A > 15-fold increase in the transfection efficiency was observed in CT26 tumor cell lines with the combination of AdALP adenovirus carrying murine granulo cyte-macrophage colony-stimulating factor (AdmGM-CSF), and liposome compare d with adenovirus alone, showing the feasibility of the combination treatme nt. In the animal model, with the combination of liposome and AdALP, deeper and wider distribution of the marker gene in the tumor mass was shown. We conclude that the limitations of direct application of adenoviral vectors i n a solid tumor model could be overcome by the use of cationic liposomes. T his approach will facilitate the more effective delivery of adenoviral vect ors in a clinical trial setting.