Evidence map›Paper›PMID 26538064›Full record

ArticleScientific reports2015

CRISPR/gRNA-directed synergistic activation mediator (SAM) induces specific, persistent and robust reactivation of the HIV-1 latent reservoirs.

Yonggang Zhang, Chaoran Yin, Ting Zhang, Fang Li, Wensheng Yang, Rafal Kaminski, Philip Regis Fagan, Raj Putatunda, Won-Bin Young, Kamel Khalili and 1 more

Abstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

106 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. CRISPR/Cas9 for achieving postintervention HIV control.Current opinion in HIV and AIDS · 2025
    Review
  7. Review
  8. Article
  9. Gene regulation technologies for gene and cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023
    Review
  20. Progress and Perspective of CRISPR-Cas9 Technology in Translational Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review

46 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Yonggang ZhangDepartment of Neuroscience, Center for Neurovirology and The Comprehensive NeuroAIDS Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140.
Chaoran YinDepartment of Neuroscience, Center for Neurovirology and The Comprehensive NeuroAIDS Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140.
Ting ZhangDepartment of Neuroscience, Center for Neurovirology and The Comprehensive NeuroAIDS Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140.
Fang LiDepartment of Neuroscience, Center for Neurovirology and The Comprehensive NeuroAIDS Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140.
Wensheng YangDepartment of Neuroscience, Center for Neurovirology and The Comprehensive NeuroAIDS Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140.
Rafal KaminskiDepartment of Neuroscience, Center for Neurovirology and The Comprehensive NeuroAIDS Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140.
Philip Regis FaganDepartment of Neuroscience, Center for Neurovirology and The Comprehensive NeuroAIDS Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140.
Raj PutatundaDepartment of Neuroscience, Center for Neurovirology and The Comprehensive NeuroAIDS Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140.
Won-Bin YoungDepartment of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219.
Kamel KhaliliDepartment of Neuroscience, Center for Neurovirology and The Comprehensive NeuroAIDS Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140.
Wenhui HuDepartment of Neuroscience, Center for Neurovirology and The Comprehensive NeuroAIDS Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140.

Funding

Viral Gene Editing and Bioinformatics Core for Institution # 269291P30MH092177 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI SHOHREH AMINI · 2011 to 2026
$24.9M
Interdisciplinary And Translational Research Training In NeurohivT32MH079785 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI Kamel Khalili · 2008 to 2026
$5.4M
Regulation of gut smooth muscle contraction and relaxation by cytokinesR01DK075964 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI HU, WENHUI · 2007 to 2016
$2.9M
RNA-mediated excision of the HIV-1 genome from latently infected cells in CNSR01NS087971 · NINDS · TEMPLE UNIV OF THE COMMONWEALTH · PI HU, WENHUI, KHALILI, KAMEL · 2014 to 2016
$1.2M
Role and mechanism of NIBP/NFkB signaling in neurogenesisR01MH101041 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI HU, WENHUI · 2013 to 2015
$594k
Development of Molecular Imaging Technology Visualizing Viral Reservoirs in VivoR21MH100949 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI YOUNG, WON-BIN · 2013 to 2014
$414k
NIDDK NIH HHS R01 DK075964NIDDK NIH HHS R01DK075964NIMH NIH HHS P30 MH092177NIMH NIH HHS P30MH092177NIMH NIH HHS R01 MH101041NIMH NIH HHS R01MH101041NIMH NIH HHS R21 MH100949NIMH NIH HHS T32 MH079785NINDS NIH HHS R01 NS087971NINDS NIH HHS R01NS087971
6 · The paper itself

Abstract

Current antiretroviral therapy does not eliminate the integrated and transcriptionally silent HIV-1 provirus in latently infected cells. Recently, a "shock and kill" strategy has been extensively explored to eradicate the HIV-1 latent reservoirs for a permanent cure of AIDS. The therapeutic efficacy of currently used agents remains disappointing because of low efficiency, non-specificity and cellular toxicity. Here we present a novel catalytically-deficient Cas9-synergistic activation mediator (dCas9-SAM) technology to selectively, potently and persistently reactivate the HIV-1 latent reservoirs. By screening 16 MS2-mediated single guide RNAs, we identified long terminal repeat (LTR)-L and O that surround the enhancer region (-165/-145 for L and -92/-112 for O) and induce robust reactivation of HIV-1 provirus in HIV-1 latent TZM-bI epithelial, Jurkat T lymphocytic and CHME5 microglial cells. This compulsory reactivation induced cellular suicide via toxic buildup of viral proteins within HIV-1 latent Jurkat T and CHME5 microglial cells. These results suggest that this highly effective and target-specific dCas9-SAM system can serve as a novel HIV-latency-reversing therapeutic tool for the permanent elimination of HIV-1 latent reservoirs.

Indexed as

Cell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsHIV-1HIV InfectionsHIV Long Terminal RepeatHumansJurkat CellsProvirusesRNA, Guide, CRISPR-Cas SystemsT-LymphocytesVirus ActivationVirus LatencyRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID26538064
PMCPMC4633726

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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.