Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Authors: Blanchard et al

Link to paper: https://www.biorxiv.org/content/10.1101/2020.04.24.060418v1.full.pdf

Journal/ Pre-Print: bioRxiv

Tags: Cell Biology, Molecular biology, Therapeutics

Research Highlights

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.

Summary

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.

Study Type

· In vitro study

· In vivo mouse study

Strengths and limitations of the paper

Novelty:

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.

Appropriate statistics:

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

Translatability:

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.

Main limitations:

· 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.