Presented by Team William_and_Mary 2020
Beteel N. Abu-Ageel¹, Avery C. Bradley¹, Matt S. Dennen¹, Riya Garg¹, Min Guo¹, Josh R. Hughes¹, Adam J. Oliver¹, Julia A. Urban¹, Wei Wang¹, Hantao Yu¹, Eric L. Bradley², Mainak J. Patel³, Margaret S. Saha§
¹iGEM Student Team Member, ²iGEM Team Secondary PI, Department of Applied Science, ³iGEM Team Secondary PI, Department of Mathematics, §iGEM Team Primary PI, Department of Biology
College of William and Mary
Williamsburg, Virginia 23185, United States
The COVID-19 pandemic has emphasized the urgent need for broad-spectrum antiviral therapies. To address this need, we have 1) designed an antiviral nasal probiotic and 2) investigated its feasibility through extensive mathematical modeling. The designed probiotic secretes polyunsaturated fatty acids (PUFAs), which may lyse viral envelopes and suppress replication by positive strand RNA viruses, in addition to regulating inflammation. Our “smart” probiotic is designed to sense excessive inflammation by detecting high levels of TNF-alpha and IFN-gamma, and to respond by switching PUFA production from arachidonic acid to anti-inflammatory docosahexaenoic acid. To determine our probiotic’s feasibility, our mathematical model quantifies the amount of PUFA produced by the probiotic, and how secreted PUFA affects viral load and cytokine production. This complex model extends beyond current probiotic models by accounting for spatial heterogeneity and transcriptional stochasticity. With our novel design and rigorous modeling, TheraPUFA provides a framework for implementing smart, living antiviral therapies.