Evidence map›Paper›PMID 34960730›Full record

ArticleViruses2021

Transient CRISPR-Cas Treatment Can Prevent Reactivation of HIV-1 Replication in a Latently Infected T-Cell Line.

Ye Liu, Rienk E Jeeninga, Bep Klaver, Ben Berkhout, Atze T Das

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

10 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. CRISPR/Cas9: a tool to eradicate HIV-1.AIDS research and therapy · 2022
    Review
  9. Article
  10. 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

5 authors at 1 institution in 1 country.

Ye LiuAmsterdam UMC, Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, University of Amsterdam, 1105AZ Amsterdam, The Netherlands.
Rienk E JeeningaAmsterdam UMC, Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, University of Amsterdam, 1105AZ Amsterdam, The Netherlands.
Bep KlaverAmsterdam UMC, Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, University of Amsterdam, 1105AZ Amsterdam, The Netherlands.
Ben BerkhoutAmsterdam UMC, Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, University of Amsterdam, 1105AZ Amsterdam, The Netherlands.
Atze T DasAmsterdam UMC, Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, University of Amsterdam, 1105AZ Amsterdam, The Netherlands.ORCID 0000-0001-7891-2315
Amsterdam University Medical Centers · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Novel therapeutic strategies aiming at the permanent inactivation of the HIV-1 reservoir in infected individuals are currently being explored, including approaches based on CRISPR-Cas gene editing. Extinction of all infectious HIV provirus in infected T-cell cultures was previously achieved when cells were transduced with lentiviral vectors for the stable expression of CRISPR-Cas9 or Cas12a systems targeting HIV DNA. Because lentiviral transduction and long-term CRISPR-Cas activity are less suitable for in vivo application of this antiviral strategy, we investigated whether HIV can also be completely inactivated by transient CRISPR-Cas activity. Latently infected SupT1 T-cells were repeatedly transfected with different Cas9 and Cas12a mRNA/protein sources in combination with dual gRNAs/crRNAs targeting highly conserved viral sequences. Upon repeated Cas9 protein treatment, viral replication could no longer be reactivated. We demonstrate that this was due to complete mutational inactivation of the proviral DNA, mostly through mutations at the target sites, but also through excision or inversion of the viral DNA fragment between the two target sites. These results demonstrate that repeated transient CRISPR-Cas treatment of a latently infected T-cell culture can lead to the permanent inactivation of HIV replication, indicating that transient CRISPR-Cas delivery methods can be considered for in vivo application.

Indexed as

CRISPR-Cas SystemsVirus ActivationCell LineDNA, ViralGene EditingHIV-1HIV InfectionsHumansLentivirusProvirusesT-LymphocytesTransduction, GeneticDNA, ViralCas12aCas9CRISPR-CasHIVRNPtransient

Identifiers

PMID34960730
PMCPMC8705111
OpenAlexW4200553026

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.