With InCanTeSiMo I aim to realize local delivery and activation of cancer-defeating synthetic circuits. Despite the advent of immunotherapy as promising treatment against a number of cancers, surgery, radio- or chemotherapy, alone or in combination, remain the most common interventions. While surgery and radiotherapy are mainly targeted to the cancer itself, chemotherapy has a systemic mode of action, affecting both healthy as well as diseased cells. An innovative way to fight cancer would be the use of synthetic circuits sensing the status of the cell into which they are delivered and acting only in response to a detected diseased status. This type of cancer therapy lends itself well to personalization, as each patient’s specific profile could be considered when designing the synthetic circuits. Since naked plasmid DNA cannot be simply released in the blood, the synthetic circuits must be encapsulated into protective vehicles, which should shield them from the immune system and accumulate them at the site of cancer. Moreover, to limit side effects due to the potential accumulation of the delivery vehicles in other body parts, it would be advantageous to locally activate the synthetic circuits with an external trigger, such as light. This would additionally allow activating the therapy at specific time points. This project comprises three major engineering efforts: 1) the establishment of cost-effective production of delivery vehicles able to specifically invade cancer cells; 2) the realization of new synthetic circuits functioning at the protein level that discern between healthy and cancer cells based on the amount of a metabolite and trigger apoptosis, or convert a pro-drug into the active drug, in the latter ones only; 3) the development of a novel red light-inducible protein-protein interaction tool.