1038. Therapy of Cancer by Inhibition of XIAP with RNAi Mediated by Tumor Specific Replicating Adenovirus

RNA interference (RNAi) induces gene silencing at a level of posttranscription mediated by double stranded RNA. Although there are numerous methods for delivery of RNAi to the target cells, the common limitation of these methods is insufficiency for gene delivery. In this study, we explored whether oncolytic adenovirus could be used as a vector to deliver RNAi to tumor cells. We have chosen to target XIAP, because over expression of XIAP has been implicated into resistance of tumor apoptosis. Our result showed that infection of tumor cells with oncolytic adenovirus carrying RNAi could inhibit XIAP expression. This effect was not observed in tumor cells infected with control vector. Furthermore, our result showed that high cytotoxicity could be induced by infection of tumor cells with oncolytic adenovirus carrying RNAi. Infection of normal cells did not induce cytopathic effect. This data indicated that oncolytic adenovirus can be used to deliver RNAi to tumor cells.