The COVID-19 pandemic, caused by SARS- CoV-2, has afflicted millions of people, with one prominent feature of its lethality being an overactive immune response, or cytokine storm. We aimed to design a synthetic mammalian network to alleviate cytokine storms using powerful, switchlike endoribonucleases. By sensing changes in concentration of two biomarkers indicative of cytokine storms, our system will respond with graded output of a cytokine-sequestering single-chain variable antibody fragment in order to differentially treat patients with varying levels of disease severity. We computationally constructed a cellular and plasma-level immune response to COVID-19 through an ODE-based SimBiology model to inform the design of our sensor specifications, network topology, and tailored treatment response. This engineered system, once experimentally verified in vitro, can be used to further our current understanding of COVID-19 immunopathology, with a particular focus on IL-1.

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MIT iGEM 2020

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