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'cause spore is more!
The treatment of diseases while avoiding systemic side effects is still a major obstacle in modern medicine. After administration, conventional drugs are distributed throughout the whole body thus affecting both, diseased and healthy cells. Current strategies on targeted drug delivery are mainly based on the applications of antibody-drug conjugates or nanoparticles. However, both approaches revealed considerable challenges in their application due to short half-life and expensive production, respectively. We developed a novel platform for targeted drug delivery by implementing highly specific nanobodies directed against surface markers of affected cells. The combination with an enzymatic functionality facilitates the local activation of prodrugs, thus preventing unnecessary side effects by systemic drug dispersal. By engineering the spores of probiotic Bacillus subtilis, a member of the human microbiome, we establish a low-cost carrier for well-tolerated treatment.
image/svg+xml Inflamed area of colon epithelium - in case of ulcerative colitis parts of colon and rectum are inflamed because of an autoimmune reaction. zellen Carcinoembryonic antigen (CEA) - in the inflamed area the expression of CEA is higher than in the healthy tissue. This makes them a perfect target for our project. CEA Carrier - Using the endospores of Bacillus subtilis as a carrier we receive a tool with multivalency. This increases the specificity of binding to diseased tissue in comparison to healthy tissue where CEA is expressed in low concentration. To gain multivalency a carrier is used. Spore Drug Delivery - Glutathione-S-Transferase is an enzyme that is responsible for several detoxification reactions in the liver. We use it locally to convert an inactive prodrug into the active drug. gst The Binding - The Nanobody, a single domain antibody, binds to the CEA with a very high specificity. With its easy production and high stability it makes the perfect binding tool for our project. nb Glutathione S-Transferase forms the reaction from the inactive prodrug azathioprine to the active 6-Mercaptopurine, which replaces adenine and guanine in the DNA and finally leads to the apoptosis of the cell. AZA
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Posted by: iGEM Freiburg

Nanocillus - 'cause spore is more!