Treating Influenza and SARS-CoV-2 via mRNA-encoded Cas13a
cell biology molecular biology therapeutics
Authors: Blanchard et al
Journal/ Pre-Print: bioRxiv
Tags: Cell Biology, Molecular biology, Therapeutics
1. Synthetic mRNA-based platform with Cas13a used to target and mitigate influenza A and SARS-CoV-2.
2. System validated to effectively degrade influenza A and SARS-CoV-2 viral RNA in vitro.
3. System validated to effectively degrade influenza A viral in an in vivo mouse model using nebulizer for mRNA delivery.
Delivery of synthetic mRNA of Cas13a and guide RNAs post-infection is sufficient to target Influenza A Virus polymerase genes and limit viral proliferation in cell-lines and a mouse model. Similar strategy but delivering Cas13A and guide RNAs prior to SARS-CoV-2 infection limits viral copies in a cell line.
Impact for SARS-CoV2/COVID19 research efforts
Possible treatment of SARS-CoV-2 positive individuals.
· In vitro study
· In vivo mouse study
Strengths and limitations of the paper
First demonstration that this approach can be used post-infection, how this approach scales with MOI and is functional over a 3-day period.
Standing in the field:
Two studies previously demonstrated ability of Cas13b or d to degrade influenza RNA. mRNA approach previously benchmarked due to not all knockdown of RNA being mediated by Cas13a.
2-way ANOVA, correct for comparing significant difference between multiple conditions.
Viral model used:
Influenza A and SARS-CoV-2 used for in vitro studies, only influenza A used for in vivo work
Show that can deliver Cas13 mRNA and guides with PBAE-based polymer via nebulizer and this is effective for treating Influenza RNA in mouse model. In vivo testing for SARS-CoV-2 still required.
· No SARS-CoV-2 in vivo data
· The Cas13a strategy was delivered prior to SARS-CoV-2 infection of a cell line
· Variations in the time post infection guides delivered and RNA levels measured.
· Fig 5: effective guides less effective in initial screen compared to detailed analysis.
· SARS-CoV-2 analysis is a very different set of experiments to that of IVA, looking more at cytopathic effect on cells than anything else.