Sensing and responding to allergic response cytokines through a genetically encoded circuit

Hélène Chassin, Barbara Geering, Lina Schukur, David Ausländer, Brian Lang and Martin Fussenegger ()
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Hélène Chassin: ETH Zürich
Barbara Geering: ETH Zürich
Lina Schukur: ETH Zürich
David Ausländer: ETH Zürich
Brian Lang: ETH Zürich
Martin Fussenegger: ETH Zürich

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract While constantly rising, the prevalence of allergies is globally one of the highest among chronic diseases. Current treatments of allergic diseases include the application of anti-histamines, immunotherapy, steroids, and anti-immunoglobulin E (IgE) antibodies. Here we report mammalian cells engineered with a synthetic signaling cascade able to monitor extracellular pathophysiological levels of interleukin 4 and interleukin 13, two main cytokines orchestrating allergic inflammation. Upon activation of transgenic cells by these cytokines, designed ankyrin repeat protein (DARPin) E2_79, a non-immunogenic protein binding human IgE, is secreted in a precisely controlled and reversible manner. Using human whole blood cell culturing, we demonstrate that the mammalian dual T helper 2 cytokine sensor produces sufficient levels of DARPin E2_79 to dampen histamine release in allergic subjects exposed to allergens. Hence, therapeutic gene networks monitoring disease-associated cytokines coupled with in situ production, secretion and systemic delivery of immunomodulatory biologics may foster advances in the treatment of allergies.

Date: 2017
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DOI: 10.1038/s41467-017-01211-1

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