Engineering of Human Commensal Bacterium for the Controlled in vivo Delivery of Human Keratinocyte Growth Factor to Trea

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Inflammatory Bowel Disease (IBD) affects 0.2% of the population in developed countries. Current therapy is restricted to drugs that suppress the body‘s immune system. These are not curative, may cause severe side effects and are likely to be needed for long periods. There is therefore a need for more targeted controlled forms of therapy. Various protein molecules have been identified as potential therapeutic factors for IBD. Due to their inherent instability and potential toxicity these factors can not be given to patients by conventional means. Recently developed genetically modified (GM) bacteria to produce and secrete various factors locally, which when administered to mouse models of IBD was as effective as steroids in preventing and treating IBD. The limitation of current bacterial delivery systems, however is that the production and release of the heterologous protein by the bacteria cannot be controlled; this is an important safety concern. Therefore, a novel approach proposed to develop a second generation of GM bacteria. This involves engineering a non pathogenic commensal bacterium to produce growth factor under the control of a naturally occurring plant product which can be included in a normal diet. We propose that the delivery of these proteins inside the bowel by GM bacteria would be safe and effective in preventing and treating IBD