Evidence map›Paper›PMID 27341108›Full record

ArticlePloS one2016

Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems.

Julia K Bialek, Gábor A Dunay, Maike Voges, Carola Schäfer, Michael Spohn, Rolf Stucka, Joachim Hauber, Ulrike C Lange

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
7.0field-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

51 citing papers in PubMed, 81 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. CRISPR/Cas9 for achieving postintervention HIV control.Current opinion in HIV and AIDS · 2025
    Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023
    Review
  12. CRISPR/Cas9: a tool to eradicate HIV-1.AIDS research and therapy · 2022
    Review
  13. HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022
    Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. CRISPR/Cas technology as a promising weapon to combat viral infections.BioEssays : news and reviews in molecular, cellular and developmental biology · 2021
    Review
  20. Broadly active zinc finger protein-guided transcriptional activation of HIV-1.Molecular therapy. Methods & clinical development · 2021
    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

8 authors at 3 institutions in 1 country.

Julia K BialekHeinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
Gábor A DunayHeinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
Maike VogesHeinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
Carola SchäferHeinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
Michael SpohnHeinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
Rolf StuckaFriedrich-Baur-Institute, Department of Neurology, Ludwig Maximilian University Munich, Munich, Germany.
Joachim HauberHeinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
Ulrike C LangeHeinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
Leibniz Institute of Virology (LIV) · DELudwig-Maximilians-Universität München · DEUniversity Medical Center Hamburg-Eppendorf · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs), act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5' long terminal repeat (LTR), for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination.

Indexed as

CRISPR-Cas SystemsGene TargetingProvirusesVirus LatencyBase SequenceBinding SitesGene EditingHIV-1HIV InfectionsHIV Long Terminal RepeatHumansJurkat CellsProtein BindingRNA, Guide, CRISPR-Cas SystemsTranscriptional ActivationVirus ReplicationRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID27341108
PMCPMC4920395
OpenAlexW2470683212

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.