Evidence map›Paper›PMID 37558852›Full record

ArticleGene therapy2024

Targeted shock-and-kill HIV-1 gene therapy approach combining CRISPR activation, suicide gene tBid and retargeted adenovirus delivery.

Sarah Klinnert, Corinne D Schenkel, Patrick C Freitag, Huldrych F Günthard, Andreas Plückthun, Karin J Metzner

Open access · hybridAbstract read
In one paragraph

Article in Gene therapy, 2024. 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
3.2field-weighted citation impact, top 8% 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, 21 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Searching for a HIV-1 Cure.Theranostics · 2026
    Review
  6. Article
  7. CRISPR/Cas9 for achieving postintervention HIV control.Current opinion in HIV and AIDS · 2025
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Advances in HIV Gene Therapy.International journal of molecular sciences · 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

6 authors at 1 institution in 1 country.

Sarah KlinnertDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.ORCID 0000-0002-1604-7917
Corinne D SchenkelDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Patrick C FreitagLife Science Zurich Graduate School, University of Zurich, Zurich, Switzerland.
Huldrych F GünthardDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Andreas PlückthunDepartment of Biochemistry, University of Zurich, Zurich, Switzerland.ORCID 0000-0003-4191-5306
Karin J MetznerDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland. Karin.Metzner@usz.ch.ORCID 0000-0003-4862-1503
University of Zurich · CH

Funding

Gilead Sciences (Gilead) 00408Novartis Foundation FN20-0000000206
6 · The paper itself

Abstract

Infections with the human immunodeficiency virus type 1 (HIV-1) are incurable due the long-lasting, latent viral reservoir. The shock-and-kill cure approach aims to activate latent proviruses in HIV-1 infected cells and subsequently kill these cells with strategies such as therapeutic vaccines or immune enhancement. Here, we combined the dCas9-VPR CRISPR activation (CRISPRa) system with gRNA-V, the truncated Bid (tBid)-based suicide gene strategy and CD3-retargeted adenovirus (Ad) delivery vectors, in an all-in-one targeted shock-and-kill gene therapy approach to achieve specific elimination of latently HIV-1 infected cells. Simultaneous transduction of latently HIV-1 infected J-Lat 10.6 cells with a CD3-retargeted Ad-CRISPRa-V and Ad-tBid led to a 57.7 ± 17.0% reduction of productively HIV-1 infected cells and 2.4-fold ± 0.25 increase in cell death. The effective activation of latent HIV-1 provirus by Ad-CRISPRa-V was similar to the activation control TNF-α. The strictly HIV-1 dependent and non-leaky killing by tBid could be demonstrated. Furthermore, the high transduction efficiencies of up to 70.8 ± 0.4% by the CD3-retargeting technology in HIV-1 latently infected cell lines was the basis of successful shock-and-kill. This novel targeted shock-and-kill all-in-one gene therapy approach has the potential to safely and effectively eliminate HIV-1 infected cells in a highly HIV-1 and T cell specific manner.

Indexed as

HIV-1HIV InfectionsAdenoviridaeCD4-Positive T-LymphocytesClustered Regularly Interspaced Short Palindromic RepeatsGenetic TherapyHumansProvirusesRNA, Guide, CRISPR-Cas SystemsVirus ActivationVirus LatencyRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID37558852
PMCPMC10940146
OpenAlexW4385698790

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.