A new spin on de novo synthesis; from DNA Chemistry to Virus

Synthetic Biology is a growing field, and on the short list for this work is the creation of viruses to improve vaccines. The hope, at least for the study highlighted here, was that through the creation of a synthetic horsepox vaccine the pox vaccine (from vaccinia at this time) could be made even safer. The research made some interesting findings, including the ability of chemically synthesized DNA for the use of rescuing horsepox virus. Synthetic DNA was cloned into circular fragments which were then chemically manipulated into overlapping DNA fragments. These fragments were split into experiments that evaluated the effectiveness of these fragments in yeast and in helper-virus infected cells. It was shown that in yeast cells, fragments resulted in the production of yeast artificial chromosomes, synthetic viruses, and a wide variety of transformation associated recombination. In the presence of helper virus to insert DNA fragments into the genome, these DNA fragments were able to synthesize virus. This sequence was selected to emulate a pox virus, but showed the capability of synthetic sequences to be inserted by virus in addition to more traditional plasmid insertion which justified the use of these techniques for the creation of potentially safer DNA virus vaccines. While this procedure has been successful for other viruses in the past, the manifestation of this work for DNA viruses, specifically pox, is extremely important. The ability for these types of cross-reactivities to exist among viral families allows for the creation of safer viruses and the creation of viral mimics that are easier to harness and study in the laboratory. Further, past work has focused on the infectious nature of RNA viruses through the introduction of the RNA genome. However, in pursuing this path of research further, it seems relevant to determine the minimum set of necessary elements in order to produce the infectious introduction and integration of these DNA fragments. In doing so, the specific role that these elements play and the interactions that they have with host cell machinery can be further studied in order to advance understanding of these viruses.

~Kyle Enriquez

Thiel V (2018) Synthetic viruses—Anything new? PLoS Pathog 14(10): e1007019. https://doi.org/10.1371/journal.ppat.1007019

Noyce RS, Lederman S, Evans DH. Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments. PLoS ONE. 2018;13(1):e0188453. pmid:29351298; PubMed Central PMCID: PMCPMC5774680.