Evidence map›Paper›PMID 29447206›Full record

ArticlePloS one2018

Multiplex CRISPR/Cas9 system impairs HCMV replication by excising an essential viral gene.

Janina Gergen, Flora Coulon, Alison Creneguy, Nathan Elain-Duret, Alejandra Gutierrez, Olaf Pinkenburg, Els Verhoeyen, Ignacio Anegon, Tuan Huy Nguyen, Franck Albert Halary and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

21 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  8. Therapeutic Applications of the CRISPR-Cas System.Bioengineering (Basel, Switzerland) · 2022
    Review
  9. Article
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  11. Review
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  13. CRISPR/Cas technology as a promising weapon to combat viral infections.BioEssays : news and reviews in molecular, cellular and developmental biology · 2021
    Review
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  15. Article
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  20. A Broad Application of CRISPR Cas9 in Infectious Diseases of Central Nervous System.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019
    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

11 authors at 3 institutions in 2 countries.

Janina GergenCentre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.
Flora CoulonCentre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.
Alison CreneguyCentre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.
Nathan Elain-DuretCentre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.
Alejandra GutierrezCIRI-International Center for Infectiology Research, Team EVIR, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, Lyon, France.
Olaf PinkenburgInstitut für medizinische Mikrobiologie, und Krankenhaushygiene, Universität Marburg, Hans-Meerwein-Strasse 2, Marburg, Germany.
Els VerhoeyenCIRI-International Center for Infectiology Research, Team EVIR, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, Lyon, France.
Ignacio AnegonCentre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.
Tuan Huy NguyenCentre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.
Franck Albert HalaryCentre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.
Fabienne HaspotCentre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.ORCID 0000-0003-0513-1387
Inserm · FRUniversité Claude Bernard Lyon 1 · FRPhilipps University of Marburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Anti-HCMV treatments used in immunosuppressed patients reduce viral replication, but resistant viral strains can emerge. Moreover, these drugs do not target latently infected cells. We designed two anti-viral CRISPR/Cas9 strategies to target the UL122/123 gene, a key regulator of lytic replication and reactivation from latency. The singleplex strategy contains one gRNA to target the start codon. The multiplex strategy contains three gRNAs to excise the complete UL122/123 gene. Primary fibroblasts and U-251 MG cells were transduced with lentiviral vectors encoding Cas9 and one or three gRNAs. Both strategies induced mutations in the target gene and a concomitant reduction of immediate early (IE) protein expression in primary fibroblasts. Further detailed analysis in U-251 MG cells showed that the singleplex strategy induced 50% of indels in the viral genome, leading to a reduction in IE protein expression. The multiplex strategy excised the IE gene in 90% of all viral genomes and thus led to the inhibition of IE protein expression. Consequently, viral genome replication and late protein expression were reduced by 90%. Finally, the production of new viral particles was nearly abrogated. In conclusion, the multiplex anti-UL122/123 CRISPR/Cas9 system can target the viral genome efficiently enough to significantly prevent viral replication.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsVirus ReplicationCell LineCytomegalovirusFlow CytometryHumansPolymerase Chain Reaction

Identifiers

PMID29447206
PMCPMC5813945
OpenAlexW2791913390

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.