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For this year's Team Slovenia iGEM project we wanted to exploit the advantages of synthetic biology for an alternative biological medical therapy which could overcome some of the difficulties connected to current biopharmaceuticals.

Each disease and its corresponding therapy is a story of its own, but we sought to design a synthetic biological solution for drug application that could be used to treat different diseases and include safety components that could be useful in different therapeutic applications.

Our solution was to engineer mammalian cells, so that they will produce and deliver biological drugs inside the organism, as if the drugs were produced by the host cells themselves. Within the engineered cells, we planned to incorporate genetic switches allowing controlled production of one or several desired therapeutics, depending on the stage of the disease. The engineered cells are incorporated in microcapsules that may be implanted into the affected tissue to ensure an immune-privileged environment for the therapeutic cells. The semi-permeable capsules allow the flux of nutrients and effector molecules through the capsule’s pores but prevent cell escape and dissemination throughout the body. For the unlikely case of cells escaping capsules, we designed a safety tag ensuring destruction of cells outside microcapsules by the patient's immune system. This form of therapy may be terminated at any given time by an outside signal inducing microcapsule degradation and therapeutic cell apoptosis in which case no traces of the exogenous material should remain in the tissue.

The main features of our proposed therapeutic device:
  1. Production of therapeutic proteins within the organism (no need for purification)
  2. Use of cell microencapsulation to allow application of the same type of engineered cells for all patients to avoid immune response, increase the reliability and predictability of the response and decrease cost
  3. Microencapsulation of cells allows localized release of therapeutic proteins in the affected tissue, which can decrease the systemic side effects
  4. Regulation of production of different therapeutic proteins appropriate for different stages of therapy. Switching between the different states of therapeutic cells is possible by a short pulse of the inducer, that can be applied to patients orally
  5. Introduction of an escape killer tag for the elimination of cells that may escape from microcapsules through augmented targeting by natural killer cells
  6. At the end of therapy the alginate microcapsule shell is degraded by a secretory alginate lyase followed by induced apoptosis of the therapeutic cells