Evidence map›Paper›PMID 37390772›Full record

ArticleEBioMedicine2023

AAV-CRISPR-Cas13 eliminates human enterovirus and prevents death of infected mice.

Choong Tat Keng, Thinesshwary Yogarajah, Regina Ching Hua Lee, Irfan Bin Hajis Muhammad, Bing Shao Chia, Suraj Rajan Vasandani, Daryl Shern Lim, Ke Guo, Yi Hao Wong, Chee Keng Mok and 2 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
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

16 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. A Chemically Induced CRISPR/dCas13Journal of medicinal chemistry · 2025
    Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. A Manual for Genome and Transcriptome Engineering.IEEE reviews in biomedical engineering · 2025
    Review
  13. Enhanced RNA-targeting CRISPR-Cas technology in zebrafish.bioRxiv : the preprint server for biology · 2024
    Article
  14. Article
  15. Article
  16. Assembling the RNA therapeutics toolbox.Medical review (2021) · 2024
    Review
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

12 authors at 2 institutions in 1 country.

Choong Tat KengGenome Institute of Singapore, Agency for Science, Technology and Research, 60 Biopolis Street, Singapore 138672, Singapore.
Thinesshwary YogarajahLaboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Infectious Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.
Regina Ching Hua LeeLaboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Irfan Bin Hajis MuhammadGenome Institute of Singapore, Agency for Science, Technology and Research, 60 Biopolis Street, Singapore 138672, Singapore.
Bing Shao ChiaGenome Institute of Singapore, Agency for Science, Technology and Research, 60 Biopolis Street, Singapore 138672, Singapore.
Suraj Rajan VasandaniGenome Institute of Singapore, Agency for Science, Technology and Research, 60 Biopolis Street, Singapore 138672, Singapore.
Daryl Shern LimGenome Institute of Singapore, Agency for Science, Technology and Research, 60 Biopolis Street, Singapore 138672, Singapore.
Ke GuoGenome Institute of Singapore, Agency for Science, Technology and Research, 60 Biopolis Street, Singapore 138672, Singapore.
Yi Hao WongNUSMed Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, 117599, Singapore.
Chee Keng MokNUSMed Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, 117599, Singapore.
Justin Jang Hann ChuInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), 61 Biopolis Drive, Proteos #06-05, 138673, Singapore; Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Infectious Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore; NUSMed Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, 117599, Singapore. Electronic address: miccjh@nus.edu.sg.
Wei Leong ChewGenome Institute of Singapore, Agency for Science, Technology and Research, 60 Biopolis Street, Singapore 138672, Singapore; Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, 117596, Singapore. Electronic address: chewwl@gis.a-star.edu.sg.
Agency for Science, Technology and Research · SGNational University of Singapore · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRNA viruses account for many human diseases and pandemic events but are often not targetable by traditional therapeutics modalities. Here, we demonstrate that adeno-associated virus (AAV) -delivered CRISPR-Cas13 directly targets and eliminates the positive-strand EV-A71 RNA virus in cells and infected mice.

methodsWe developed a Cas13gRNAtor bioinformatics pipeline to design CRISPR guide RNAs (gRNAs) that cleave conserved viral sequences across the virus phylogeny and developed an AAV-CRISPR-Cas13 therapeutics using in vitro viral plaque assay and in vivo EV-A71 lethally-infected mouse model.

findingsWe show that treatment with a pool of AAV-CRISPR-Cas13-gRNAs designed using the bioinformatics pipeline effectively blocks viral replication and reduces viral titers in cells by >99.99%. We further demonstrate that AAV-CRISPR-Cas13-gRNAs prophylactically and therapeutically inhibited viral replication in infected mouse tissues and prevented death in a lethally challenged EV-A71-infected mouse model.

interpretationOur results show that the bioinformatics pipeline designs efficient CRISPR-Cas13 gRNAs for direct viral RNA targeting to reduce viral loads. Additionally, this new antiviral AAV-CRISPR-Cas13 modality represents an effective direct-acting prophylactic and therapeutic agent against lethal RNA viral infections.

fundingAgency for Science, Technology and Research (A∗STAR) Assured Research Budget, A∗STAR Central Research Fund UIBR SC18/21-1089UI, A∗STAR Industrial Alignment Fund Pre-Positioning (IAF-PP) grant H17/01/a0/012, MOE Tier 2 2017 (MOE2017-T2-1-078; MOE-T2EP30221-0005), and NUHSRO/2020/050/RO5+5/NUHS-COVID/4.

Indexed as

COVID-19EnterovirusEnterovirus A, HumanAnimalsCRISPR-Cas SystemsDependovirusHumansMiceAdeno-associated viral vectorsBioinformaticsCRISPR-Cas13dEnterovirusProphylacticTherapeutic

Identifiers

PMID37390772
PMCPMC10363442
OpenAlexW4382361023

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.