Self-replicating RNAs as a pipeline for discovery

Self-replicating RNAs as a pipeline for discovery. The process of evolution provides unthinkable adaptability through the continual diversification of a parental design. As such, we utilize this framework to generate a novel discovery platform by exploiting the capacity of a self-replicating RNA element to diversify both natural and random genetic designs. More specifically, we utilize the relative poor fidelity of an RNA dependent RNA polymerase (RdRp) to discover new antibiotics and antivirals. Our technical approaches focus on RdRps encoded on a single RNA element flanked by recognition motifs to enable autonomous replication. This biocontained artificial self-amplifying chimeric RNA (BASiC RNA) not only amplifies its own open reading frame, but it also transcribes multiple sub-genomic fragments that can be engineered to express any desired biosynthetic gene clusters of interest. We are presently exploring the use of this technology to generate new biological materials for a wide array of applications.