A safe synthetic probiotic expression system for antibodies.

Noroviruses (NoV) are cause of epidemic outbreaks of gastrointestinal illness. Even if they are considered as a moderate threat – classified as category B pathogens by the National Institute of Allergy and Infectious diseases – the spreading speed of these pathogens is dramatic: rates of reported NoV outbreaks reach 21 million cases of acute gastroenteritis per year, 70.000 of those need hospitalization and 800 die. This is due to a rapid person-to-person transmission in semi-closed places like hospital, school and public transports. Moreover it seems that it is really difficult to develop an immunological memory against NoV that avoids further illness.

Our project aims to build a probiotic bacteria that helps the immune system to fight this pathogenic agent. First of all we had to choose a suitable bacterial strain for the gut environment that can easily be manipulated. Than we had to face an important issue: safety. For this purpose we designed a robust gene guard system regulated by a novel inducible switch and by an human antimicrobial peptide that can destroy, in any moment, the bacteria and avoid the transgene horizontal exchange.

Finally we will provide to our bacteria a weapon able to capture and inactivate our target thanks to a synthetic minibody fused to a protein membrane. This feature can be slightly modified to target any other pathogenic agent with enteric tropism.

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Modeling meeting

We've met with our modeling advisor, and we now have a theoretical model that we can try to fit some experimental data on!