A collaboration of scientists from Switzerland and France recently reported in Synthetic Biology on the successful restoration of normal skin tissue morphology in psoriatic mice implanted with microencapsulated cytokine converter transgenic designer cells. In addition to significantly improving the appearance of current lesions, the implants also prevented future flares.
The rationale for the development of synthetic cytokine converter cell implant technology was to work within the immune system to detect metabolic disturbances and trigger natural immune responses to normalize them. The implant was designed to detect simultaneous elevations of 2 kinds of designated cytokines in order to initiate a metabolic therapeutic response.
While the technology can easily be applied to any chronic systemic disorder with reliable circulating biomarkers of disease activity, the investigators chose to study its potential efficacy first in psoriasis, an autonomic disorder specifically associated with excess expression of tumor necrosis factor (TNF) and interleukin-22 (IL-22). The implanted cells use Boolean AND gate logic to monitor circulation of TNF and IL-22 together, to detect and quantify elevations of both, and to subsequently produce and deliver appropriate therapeutic doses of IL-4 and IL-10 exclusively in a response that resets the metabolic system.
In their experiments, the investigators first validated the cytokine-response dynamics of human cells. The specificity to TNF and IL-22 cells responsible for psoriatic inflammation was then demonstrated in in vivo studies of implanted mice by a significant activation of the cytokine converter cells in those with psoriasis induced by the immune response modifier imiquimod compared with normal implanted controls. The synthetic cytokine converter cells were shown in the multiphase investigation to be specific to these proteins while remaining insensitive to bacterial and viral infection, as well as skin inflammation of non-psoriatic origin.
The cytokine converter successfully prevented flare-ups in the mice and produced even higher levels of IL-4 and IL-10 in response to established psoriasis; however, the investigators cited a number of design hurdles in adapting the cytokine converter cells for clinical trials.
The authors contend that “these synthetic circuits, which program designer cells to process complete metabolic information, open the door to autonomously prevent, attenuate, or reset acute or chronic medical conditions.” Cytokine converter cell implant technology represents a translational approach to largely curing chronic inflammatory diseases like psoriasis.
- Schukur L, Geering B, Charpin-El Hamri G, Fussenegger M. Implant able synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis. Synthetic Biology. 2015;7(318):318ra201.