The genome of a double-stranded RNA virus is edited for the first time

Oscar Burrone, ICGEB Trieste, Italy, and collaborators have published findings on the first nuclease-mediated genome editing of Rotavirus, a double-stranded RNA virus, in Cell Reports.

A research team led by Oscar Burrone has reported the first nuclease-mediated editing of the genome of rotavirus, one of the main pathogens for humans and livestock with a double-stranded RNA genome. Achieved by engineering a CRISPR-derived molecular scissor – Csy4 – to localise viral factories inside rotavirus, this molecular approach has revealed a previously unknown ability of viruses to repair their genome.

While CRISPR nucleases have been used to modify almost any type of genome, not all types of genomes can be CRISPR-engineered. In the paper published in Cell Press by Guido Papa, MRC Molecular Biology Lab, Cambridge UK, et al, this last frontier in the genome-editing field has been crossed.

“Repair is not perfect, but contains an edited viral RNA genome sequence”, confirms Papa, “taking advantage of our newly-developed CRISPR-based technology, we shed light on a critical aspect of Rotavirus replication secondary transcription, showing that this is the main source of rotavirus pathogenicity”.

Lead author, Oscar Burrone, underlines the future application of this study: “Csy4-mediated Rotavirus genome editing is a platform that paves the way for the development of new therapeutics targeting fundamental steps of Rotavirus replication. As the current COVID19 pandemic illustrates, viruses can never be underestimated and we need to seek vanguard approaches to develop innovative antiviral drugs”.

“Bacteria have naturally developed a number of CRISPR systems to fight incoming viruses; we selected CRISPR-Csy4 to push previous limits and to edit double stranded RNA viral genomes” says Gianluca Petris (co-author on this paper).

Scientific Article:

Papa, G., Venditti, L., Braga, L., Giacca, M., Petris, G., Burrone, O.R. 2020. CRISPR-Csy4-mediated editing of rotavirus double-stranded RNA genome. Cell Reports DOI: [Open Access]