Implantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis

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Science Translational Medicine  16 Dec 2015:
Vol. 7, Issue 318, pp. 318ra201
DOI: 10.1126/scitranslmed.aac4964

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A psoriatic switch

Taking pills may go the way of the horse and buggy, the rotary phone, and the Walkman, at least if synthetic biology has anything to say about it. Schukur et al. designed a circuit that would automatically sense the presence of two disease-causing molecules, called cytokines, in the body and respond by triggering the production of two other cytokines that would treat the disease. This circuit was genetically engineered in a mammalian cell; in turn, the cell was implanted in mice with psoriasis—an inflammatory skin condition that has no cure. When levels of the proinflammatory cytokines TNF and IL22 peaked in the body, the synthetic circuit kicked into gear, converting these cytokine signals into an anti-inflammatory cellular output, consisting of IL4 and IL10, which then attenuated disease. The “cytokine converter” cells not only prevented psoriasis flare-ups, as they’re called, but also treated acute (established) psoriasis, returning skin to normal in mice. In demonstrating that the converter cells were responsive to blood from psoriasis patients, the authors suggest that synthetic biology may be ready to autonomously flip therapeutic switches in people and later take on other diseases with defined disease indicators.