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iGEM Manchester-Graz - Design

Applied Design

iGEM Manchester-Graz’s took the first steps in the development of a novel technology for drug delivery by developing self-regulating, drug-producing bacteria. In the near future, they could be incorporated into patients’ gut micro flora to secrete medicines directly inside the body. We focused on the late stage treatment of Parkinson’s disease, for which the current treatment involves the oral administration of L-DOPA. Our talks with experts (Interviews) in the medical field showed that one of the common side effects of oral L-DOPA treatment is rapid depletion of the jejunum, were L-DOPA is mainly absorbed. Consequently L-DOPA cannot continue to be administered orally and a PEG-PEJ tube needs to be installed surgically. This way L-DOPA is injected continuously direct into the jejunum in lower concentrations (20-200mg/h) via an external pump. This so called Duodopa® therapy is not only a massive decrease in quality of life for patients, but treatment costs also accumulate to over $100,000 a year per person. (Interview with Dr. Högenauer)

human gut bacteria
Fig 1 Administration of L-DOPA via bacteria in the patient's gut

By working closely together with patients, experts in medicine and industry representatives we tried to design the system in the most effective way. Our regulatory system is designed to produce L-DOPA in vivo in the jejunum using probiotic bacteria such as E. coli Nissle 1917. Our Modeling Results indicate that our system is capable of producing up to 81.9 mg/h/L, which would be more than sufficient to replace Duodopa® therapy. We focused our work on the treatment of Parkinson’s disease to give patients hope for a better life. Additionally, the system is also capable of various other applications (Collaboration). Our collaborations with UCL iGEM and Norwich iGEM showed that the system is also easy to apply in other single or multi gene pathways.

Furthermore, the talks to industry representatives and further investigations showed that the system can also be used as a green alternative to current chemical processes producing Dopamine or L-DOPA in the pharmaceutical industry. A greener industrial process leads to sustainable handling of natural resources and much lower waste removal or recycling costs (Industry).