Evidence map›Paper›PMID 38839984›Full record

ArticleNature microbiology2024

mRNA-encoded Cas13 can be used to treat dengue infections in mice.

Mausumi Basu, Chiara Zurla, Tabassum T Auroni, Daryll Vanover, Lorena C S Chaves, Heena Sadhwani, Heather Pathak, Rahul Basu, Jared P Beyersdorf, Oluwatomi O Amuda and 10 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature microbiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Mausumi Basu *Department of Biology, Georgia State University, Atlanta, GA, USA.
Chiara Zurla *Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
Tabassum T Auroni *Department of Biology, Georgia State University, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-5929-2728
Daryll VanoverWallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
Lorena C S ChavesWallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
Heena SadhwaniDepartment of Biology, Georgia State University, Atlanta, GA, USA.
Heather PathakDepartment of Biology, Georgia State University, Atlanta, GA, USA.
Rahul BasuDepartment of Biology, Georgia State University, Atlanta, GA, USA.
Jared P BeyersdorfWallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
Oluwatomi O AmudaDepartment of Biology, Georgia State University, Atlanta, GA, USA.
Amany ElsharkawyDepartment of Biology, Georgia State University, Atlanta, GA, USA.
Varun MosurWallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
Robert A ArthurEmory Integrated Computational Core, Emory University, Atlanta, GA, USA.
Henry ClaussenEmory Integrated Computational Core, Emory University, Atlanta, GA, USA.
Loren E SasserWallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
Jay A WroeWallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-9311-336X
Hannah E PeckWallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
Mukesh KumarDepartment of Biology, Georgia State University, Atlanta, GA, USA. mkumar8@gsu.edu.ORCID http://orcid.org/0000-0003-0970-4875
Margo A BrintonDepartment of Biology, Georgia State University, Atlanta, GA, USA. mbrinton@gsu.edu.ORCID http://orcid.org/0000-0003-4868-175X
Philip J SantangeloWallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA. philip.j.santangelo@emory.edu.ORCID http://orcid.org/0000-0001-7352-0339

Funding

United States Department of Defense | Defense Advanced Research Projects Agency (DARPA) HR0011-19-2-0008
6 · The paper itself

Abstract

Dengue is a major global health threat, and there are no approved antiviral agents. Prior research using Cas13 only demonstrated dengue mitigation in vitro. Here we demonstrate that systemic delivery of mRNA-encoded Cas13a and guide RNAs formulated in lipid nanoparticles can be used to treat dengue virus (DENV) 2 and 3 in mice. First, we identified guides against DENV 2 and 3 that demonstrated in vitro efficacy. Next, we confirmed that Cas13 enzymatic activity is necessary for DENV 2 or DENV 3 mitigation in vitro. Last, we show that a single dose of lipid-nanoparticle-formulated mRNA-encoded Cas13a and guide RNA, administered 1 day post-infection, promotes survival of all infected animals and serum viral titre decreases on days 2 and 3 post-infection after lethal challenge in mice. Off-target analysis in mice using RNA sequencing showed no collateral cleavage. Overall, these data demonstrate the potential of mRNA-encoded Cas13 as a pan-DENV drug.

Indexed as

Antiviral AgentsDengueDengue VirusDisease Models, AnimalNanoparticlesRNA, MessengerAnimalsCRISPR-Associated ProteinsFemaleHumansLipidsLiposomesMiceRNA, Guide, CRISPR-Cas SystemsViral LoadAntiviral AgentsCRISPR-Associated ProteinsLipid NanoparticlesLipidsLiposomesRNA, Guide, CRISPR-Cas SystemsRNA, Messenger

Identifiers

PMID38839984

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.