Editors' ChoiceSynthetic Biology

A psoriatic switch

Sci. Signal.  22 Dec 2015:
Vol. 8, Issue 408, pp. ec380
DOI: 10.1126/scisignal.aaf1057

Taking pills may go the way of the horse and buggy, 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 the amounts of the proinflammatory cytokines TNF and IL-22 peaked in the body, the synthetic circuit turned on, converting these cytokine signals into an anti-inflammatory cellular output, consisting of IL-4 and IL-10, which then attenuated disease. The “cytokine converter” cells not only prevented psoriasis “flare-ups” but also treated acute 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.

L. Schukur, B. Geering, G. Charpin-El Hamri, M. Fussenegger, Implantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis. Sci. Transl. Med. 7, 318ra201 (2015). [Abstract]