Related Experiment Video
Updated: Jun 23, 2026
Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Treatment of influenza and SARS-CoV-2 infections via mRNA-encoded Cas13a in rodents
Emmeline L Blanchard1, Daryll Vanover1, Swapnil Subhash Bawage1
1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
Abstract:
Cas13a has been used to target RNA viruses in cell culture, but efficacy has not been demonstrated in animal models. In this study, we used messenger RNA (mRNA)-encoded Cas13a for mitigating influenza virus A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mice and hamsters, respectively. We designed CRISPR RNAs (crRNAs) specific for PB1 and highly conserved regions of PB2 of influenza virus, and against the replicase and nucleocapsid genes of SARS-CoV-2, and selected the crRNAs that reduced viral RNA levels most efficiently in cell culture. We delivered polymer-formulated Cas13a mRNA and the validated guides to the respiratory tract using a nebulizer. In mice, Cas13a degraded influenza RNA in lung tissue efficiently when delivered after infection, whereas in hamsters, Cas13a delivery reduced SARS-CoV-2 replication and reduced symptoms. Our findings suggest that Cas13a-mediated targeting of pathogenic viruses can mitigate respiratory infections.
Insights
Messenger RNA (mRNA)-encoded Cas13a effectively targeted influenza and SARS-CoV-2 in animal models. This CRISPR-based therapy shows promise for mitigating respiratory viral infections.
Area of Science:
- Molecular Biology
- Virology
- Gene Editing
Background:
- Cas13a has shown potential for targeting RNA viruses in vitro.
- Efficacy of Cas13a in animal models for viral mitigation remains largely unproven.
Purpose of the Study:
- To evaluate the efficacy of messenger RNA (mRNA)-encoded Cas13a in mitigating influenza A virus and SARS-CoV-2 infections in animal models.
- To assess the delivery of Cas13a mRNA and CRISPR RNAs (crRNAs) to the respiratory tract via nebulization.
Main Methods:
- Designed and selected crRNAs targeting conserved regions of influenza virus (PB1, PB2) and SARS-CoV-2 (replicase, nucleocapsid genes).
- Delivered polymer-formulated Cas13a mRNA and crRNAs to the respiratory tract of mice and hamsters using a nebulizer.
- Assessed viral RNA levels, viral replication, and clinical symptoms post-treatment.
Main Results:
- Cas13a efficiently degraded influenza RNA in mouse lung tissue after infection.
- Cas13a delivery reduced SARS-CoV-2 replication and alleviated symptoms in hamsters.
- Nebulized delivery of mRNA-encoded Cas13a proved effective in both animal models.
Conclusions:
- mRNA-encoded Cas13a demonstrates efficacy in mitigating respiratory viral infections in vivo.
- Cas13a-mediated RNA targeting offers a potential therapeutic strategy against pathogenic viruses.
- Nebulizer-based delivery is a viable method for respiratory tract gene therapy applications.
More Related Videos
13:45A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia
Published on: September 21, 2019
08:41Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
