Apr 24, 2020

Treating Influenza and SARS-CoV-2 via mRNA-encoded Cas13a

BioRxiv : the Preprint Server for Biology
E. L. BlanchardPhilip J Santangelo

Abstract

Here, Cas13a has been used to target and mitigate influenza virus A (IAV) and SARS-CoV-2 using a synthetic mRNA-based platform. CRISPR RNAs (crRNA) against PB1 and highly conserved regions of PB2 were screened in conjunction with mRNA-encoded Cas13a. Screens were designed such that only guides that decreased influenza RNA levels in a Cas13-mediated fashion, were valid. Cas13a mRNA and validated guides, delivered post-infection, simulating treatment, were tested in combination and across multiplicities of infection. Their function was also characterized over time. Similar screens were performed for guides against SARS-CoV-2, yielding multiple guides that significantly impacted cytopathic effect. Last, the approach was utilized in vivo, demonstrating the ability to degrade influenza RNA in a mouse model of infection, using polymer-formulated, nebulizer-based mRNA delivery. Our findings demonstrate the applicability of Cas13a in mitigating respiratory infections both in vitro and in a mouse model, paving the way for future therapeutic use.

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Mentioned in this Paper

BRCA2 Protein
Study
Germ-Line Mutation
Epithelial Ovarian Cancer
Ovarian Carcinoma
Cancer Treatment
Breast
Salpingo-oophorectomy
BRCA2
Simulation

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