Computational design of a Dengue virus sensor

BRIAN BOKSER; FRANCO TAVELLA; ARIEL APTEKMANN; MARIA JOSE GATTAS

Congreso; ISCB-Latin America 2016; 2016

ISCB - LA

Dengue fever is a mosquito-borne virus disease that causes 390 millions of infections every year. Its diagnosis is typically clinical and it?s difficult to differentiate from other viral infections such as Zika and Chikungunya fever. Early diagnosis reduces fatality rate considerably and serves as an epidemiological tool. Modern laboratory techniques are either too expensive or too slow to be applied efficiently. Toehold switches, with their wide dynamic range, orthogonality, and programmability, represent an interesting platform for the translation regulation. We propose a viral sensor, based on a this kind of riboswitches, which tackles all these issues. We designed a set of four riboswitches that detect hallmark sequences of each strain of the dengue virus. To this purpose we developed a design protocol that includes traditional toehold design but targets the least conserved sequences in the viral genome. These sequences are characteristic of each strain and are not present on other viruses. Our method is based on secondary structure equilibrium and binding competition that maximizes orthogonality and sensibility.Currently we are testing our design in vivo under Escherichia Coli through the expression of GFP. There is still a necessity for better toehold design tools to enhance its qualities and explore their capabilities.