Swiss and German researchers have developed a yeast-based synthetic genomics platform that can rapidly reconstruct diverse RNA viruses, including SARS-CoV-2, the virus behind the current COVID-19 pandemic. The study, published in Nature, has allowed researchers to gain insights into viral pathogenesis and vaccine development.
Large RNA virus genomes, such as those in coronaviruses, are difficult to clone and manipulate in E.coli as they’re too large and can be unstable. Therefore, as an alternative, the researchers developed a yeast-based synthetic genomes platform that can genetically reconstruct RNA viruses.
They created viral subgenomic fragments using viral isolates, cloned viral DNA, and clinical samples of synthetic DNA. This was reassembled in one step in Saccharomyces cerevisiae using transformation associated recombination (TAR) cloning. This technique maintained the viral genome as a yeast artificial chromosome (YAC).
The authors wrote that by using this platform they were able to engineer and resurrect chemically synthesised clones of the recent SARS-CoV-2 in only a week after receiving the synthetic DNA fragments. This enables a rapid response to emerging viruses as it allows for the generation and functional characterisation of evolving RNA virus variants in real-time during an outbreak.
Generating SARS-CoV-2 from chemically synthesised DNA could help to bypass the limited availability of virus isolates and allow for genetic modifications and functional characterisation.