![]() 2 Of those, monoclonal antibodies targeting tumor necrosis factor (TNF) have become a cornerstone of IBD therapy. 1 Several biologics and small-molecule inhibitors were developed to inhibit the pathological activity of the various cytokine pathways. Its exact pathomechanism is not known, but it is well established that cytokines play a central role in the development of the disease. It is characterized by recurrent inflammation of the gastrointestinal tract and has serious, potentially lethal consequences. ![]() Inflammatory bowel disease (IBD) is an often severe, chronic disease of the colon and small intestine. ![]() With further safety modifications this method could serve as a safe and side effect-free alternative to biologicals targeting TNF or other inflammatory mediators. The expression levels of TNF and other cytokines significantly decreased upon this treatment in dextran sulfate sodium (DSS)-induced colitis, and the degree of inflammation was significantly reduced. This allowed the delivery of a plasmid encoding small hairpin RNA (shRNA) targeting tumor necrosis factor (TNF) into the cytoplasm of the target cells. These proteins enabled the bacteria first to invade the colon epithelium and then degrade in the phagosome. This bacterium-mediated RNA interference strategy was based on the genomically stable, non-pathogenic E. coli MDS42 strain, which was engineered to constitutively produce invasin and the listeriolysin O cytolysin. We developed an orally administered, engineered, bacterium-based, RNA interference-mediated therapeutic method to significantly reduce the symptoms in the most frequently used animal model of inflammatory bowel disease.
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