Evidence map›Paper›PMID 35879545›Full record

ArticleNature chemical biology2022

Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection.

Zhifen Cui, Cong Zeng, Furong Huang, Fuwen Yuan, Jingyue Yan, Yue Zhao, Yufan Zhou, William Hankey, Victor X Jin, Jiaoti Huang and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
5.6field-weighted citation impact, top 3% 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

42 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Precise progerin targeting using RfxCas13d: A therapeutic avenue for Hutchinson-Gilford progeria syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. CRISPR-epigenetic crosstalk: From bidirectional regulation to therapeutic potential.Computational and structural biotechnology journal · 2025
    Review
  16. Article
  17. Enhanced RNA-targeting CRISPR-Cas technology in zebrafish.bioRxiv : the preprint server for biology · 2024
    Article
  18. LPANano research · 2024
    Article
  19. Review
  20. Lung-specific supramolecular nanoparticles for efficient delivery of therapeutic proteins and genome editing nucleases.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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

17 authors at 3 institutions in 2 countries.

Zhifen CuiDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0002-5223-930X
Cong ZengViruses and Emerging Pathogens Program, Infectious Diseases Institute, Center for Retrovirus Research and Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0003-4423-3634
Furong HuangDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Fuwen YuanDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Jingyue YanDivision of Pharmaceutics and Pharmacology, College of Pharmacy and Department of Biomedical Engineering, The Ohio State University, Columbus, OH, USA.
Yue ZhaoDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0002-0110-0359
Yufan ZhouDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-8385-433X
William HankeyDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Victor X JinDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-8765-3471
Jiaoti HuangDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Herman F StaatsDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Jeffrey I EverittDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0003-0273-6284
Gregory D SempowskiDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Hongyan WangDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Yizhou DongDivision of Pharmaceutics and Pharmacology, College of Pharmacy and Department of Biomedical Engineering, The Ohio State University, Columbus, OH, USA. dong.525@osu.edu.ORCID http://orcid.org/0000-0001-5786-0659
Shan-Lu LiuViruses and Emerging Pathogens Program, Infectious Diseases Institute, Center for Retrovirus Research and Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA. liu.6244@osu.edu.ORCID http://orcid.org/0000-0003-1620-3817
Qianben WangDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA. qianben.wang@duke.edu.ORCID http://orcid.org/0000-0003-2636-7145
Duke University · USThe Ohio State University · USThe University of Texas Health Science Center at San Antonio · US

Funding

Regional Biocontainment Laboratory (RBL)UC6AI058607 · NIAID · DUKE UNIVERSITY · PI WILLIAMS, R SANDERS · 2003 to 2005
$16.3M
Project 3: Responding to Changing Serological and Viral Information around COVID-19 (RESPOND)U54CA260582 · NCI · OHIO STATE UNIVERSITY · PI MCALEARNEY, ANN SCHECK, OLTZ, EUGENE M · 2020 to 2024
$10.4M
Systems Analysis of Epigenomic Architecture in Cancer ProgressionU54CA217297 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI JIN, VICTOR · 2017 to 2021
$9.3M
Omics analysis of three-dimensional transcriptional regulationR01GM114142 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI JIN, VICTOR, LIN, SHILI · 2015 to 2024
$2.7M
Construction of in vivo mRNA delivery systemsR35GM144117 · NIGMS · OHIO STATE UNIVERSITY · PI Yizhou Dong · 2022 to 2026
$2.4M
TIM-mediated Inhibition of HIV Release: Cooperation with SERINC and Antagonism by NefR01AI150473 · NIAID · OHIO STATE UNIVERSITY · PI LIU, SHAN-LU · 2019 to 2021
$995k
NCI NIH HHS U54 CA217297NCI NIH HHS U54 CA260582NIAID NIH HHS R01 AI150473NIAID NIH HHS UC6 AI058607NIGMS NIH HHS R01 GM114142NIGMS NIH HHS R35 GM144117
6 · The paper itself

Abstract

SARS-CoV-2 entry into cells requires specific host proteases; however, no successful in vivo applications of host protease inhibitors have yet been reported for treatment of SARS-CoV-2 pathogenesis. Here we describe a chemically engineered nanosystem encapsulating CRISPR-Cas13d, developed to specifically target lung protease cathepsin L (Ctsl) messenger RNA to block SARS-CoV-2 infection in mice. We show that this nanosystem decreases lung Ctsl expression in normal mice efficiently, specifically and safely. We further show that this approach extends survival of mice lethally infected with SARS-CoV-2, correlating with decreased lung virus burden, reduced expression of proinflammatory cytokines/chemokines and diminished severity of pulmonary interstitial inflammation. Postinfection treatment by this nanosystem dramatically lowers the lung virus burden and alleviates virus-induced pathological changes. Our results indicate that targeting lung protease mRNA by Cas13d nanosystem represents a unique strategy for controlling SARS-CoV-2 infection and demonstrate that CRISPR can be used as a potential treatment for SARS-CoV-2 infection.

Indexed as

COVID-19 Drug TreatmentAnimalsCathepsin LChemokinesCytokinesEndopeptidasesLungMicePeptide HydrolasesProtease InhibitorsRNA, MessengerSARS-CoV-2Cathepsin LChemokinesCytokinesEndopeptidasesPeptide HydrolasesProtease InhibitorsRNA, Messenger

Identifiers

PMID35879545
PMCPMC10082993
OpenAlexW4287510521

What OpenQuestion holds

Textmetadata
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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.