Evidence map›Paper›PMID 27528385›Full record

ArticleScientific reports2016

Negative Feedback Regulation of HIV-1 by Gene Editing Strategy.

Rafal Kaminski, Yilan Chen, Julian Salkind, Ramona Bella, Won-Bin Young, Pasquale Ferrante, Jonathan Karn, Thomas Malcolm, Wenhui Hu, Kamel Khalili

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

40 citing papers in PubMed, 58 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. CRISPR-Cas12b enables a highly efficient attack on HIV proviral DNA in T cell cultures.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023
    Article
  7. Article
  8. Article
  9. CRISPR editing of CCR5 and HIV-1 facilitates viral elimination in antiretroviral drug-suppressed virus-infected humanized mice.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  10. A CRISPR-Cas Cure for HIV/AIDS.International journal of molecular sciences · 2023
    Review
  11. Article
  12. Article
  13. CRISPR/Cas9: a tool to eradicate HIV-1.AIDS research and therapy · 2022
    Review
  14. Article
  15. HIV-1 cure strategies: why CRISPR?Expert opinion on biological therapy · 2021
    Review
  16. CRISPR/Cas technology as a promising weapon to combat viral infections.BioEssays : news and reviews in molecular, cellular and developmental biology · 2021
    Review
  17. CRISPR-Cas9: A Preclinical and Clinical Perspective for the Treatment of Human Diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Review
  18. Review
  19. Article
  20. MultiplexedViruses · 2020
    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

10 authors at 3 institutions in 1 country.

Rafal KaminskiDepartment of Neuroscience Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor Philadelphia, PA 19140, USA.
Yilan ChenDepartment of Neuroscience Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor Philadelphia, PA 19140, USA.
Julian SalkindDepartment of Neuroscience Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor Philadelphia, PA 19140, USA.
Ramona BellaDepartment of Neuroscience Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor Philadelphia, PA 19140, USA.
Won-Bin YoungDepartment of Radiology University of Pittsburgh School of Medicine Pittsburgh, PA 15219, USA.
Pasquale FerranteDepartment of Neuroscience Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor Philadelphia, PA 19140, USA.
Jonathan KarnDepartment of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH 44106, USA.
Thomas MalcolmExcision Biotherapeutics, Inc., 3624 Market Street, #514, Philadelphia, PA 19104, USA.
Wenhui HuDepartment of Neuroscience Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor Philadelphia, PA 19140, USA.
Kamel KhaliliDepartment of Neuroscience Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor Philadelphia, PA 19140, USA.
Temple University · USCase Western Reserve University · USUniversity of Pittsburgh · US

Funding

Viral Gene Editing and Bioinformatics Core for Institution # 269291P30MH092177 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI Kamel Khalili · 2011 to 2026
$24.9M
Project 3 Dysregulation of metabolic communication of oligodendrocytes and neurons by cocaine and TatP01DA037830 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI KHALILI, KAMEL · 2015 to 2019
$7.4M
Regulation of HIV-1 by Rad51 in CNS cellsR01MH093271 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI KHALILI, KAMEL · 2011 to 2015
$1.9M
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
Identification of receptors for transcytotic delivery of therapeutic agents crossing the BBBR21NS094084 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI EDWARDS, WILSON BARRY, YOUNG, WON-BIN · 2016 to 2017
$426k
Development of Molecular Imaging Technology Visualizing Viral Reservoirs in VivoR21MH100949 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI YOUNG, WON-BIN · 2013 to 2014
$414k
NIDA NIH HHS P01 DA037830NIMH NIH HHS P30 MH092177NIMH NIH HHS R01 MH093271NIMH NIH HHS R21 MH100949NINDS NIH HHS R01 NS087971
6 · The paper itself

Abstract

The CRISPR/Cas9 gene editing method is comprised of the guide RNA (gRNA) to target a specific DNA sequence for cleavage and the Cas9 endonuclease for introducing breaks in the double-stranded DNA identified by the gRNA. Co-expression of both a multiplex of HIV-1-specific gRNAs and Cas9 in cells results in the modification and/or excision of the segment of viral DNA, leading to replication-defective virus. In this study, we have personalized the activity of CRISPR/Cas9 by placing the gene encoding Cas9 under the control of a minimal promoter of HIV-1 that is activated by the HIV-1 Tat protein. We demonstrate that functional activation of CRISPR/Cas9 by Tat during the course of viral infection excises the designated segment of the integrated viral DNA and consequently suppresses viral expression. This strategy was also used in a latently infected CD4+ T-cell model after treatment with a variety of HIV-1 stimulating agents including PMA and TSA. Controlled expression of Cas9 by Tat offers a new strategy for safe implementation of the Cas9 technology for ablation of HIV-1 at a very early stage of HIV-1 replication during the course of the acute phase of infection and the reactivation of silent proviral DNA in latently infected cells.

Indexed as

Gene EditingGene Expression Regulation, Viral3' Untranslated Regions5' Untranslated RegionsBase SequenceCD4-Positive T-LymphocytesClustered Regularly Interspaced Short Palindromic RepeatsGenes, ViralHIV-1HIV Long Terminal RepeatHumansJurkat CellsPromoter Regions, GeneticSequence Homology, Nucleic AcidVirus Replication3' Untranslated Regions5' Untranslated Regions

Identifiers

PMID27528385
PMCPMC4985742
OpenAlexW4249951088

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.