Therapeutic DNA vaccination and RNA interference in inflammatory bowel disease

Abstract

Angiogenesis plays a significant role in numerous diseases. Recently, dysbalanced angiogenesis was found to be a component of pathogenesis of inflammatory bowel disease (IBD). Therefore, inhibition of angiogenesis is a novel therapeutic strategy that alleviates the inflammation and clinical outcomes of IBD. Bacteria act as vectors for the delivery of therapeutic sequences, a process that is particularly suitable in IBD, due to the natural occurrence of bacteria in gut. The main focus of the present study was the application of bacterial gene therapy in the modulation of angiogenesis in IBD. As a target molecule we used the main proangiogenic factor, vascular endothelial growth factor (VEGF). Bacterial strain Salmonella typhimurium SL7207 was used as a gene delivery vector for oral application. DNA vaccination and RNA interference were examined and their efficiency in improving the course of the disease in dextran sulfate sodium-induced colitis in mice was compared. The two approaches yielded similar beneficial results in evaluation of the disease activity parameters (stool consistency, weight loss and colon length) as well as VEGF expression and tumor necrosis factor-α (TNF-α). Improvement in all of the parameters compared with the control groups not treated by therapeutic bacterial strains was also observed. All the bacterial groups showed similar improvement in histopathological scoring. Results of this study are consistent with the literature and provide a basis for additional studies on the modulation of angiogenesis in IBD.