Evidence map›Paper›PMID 24162716›Full record

ArticleBlood2014

Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection.

Chuka A Didigu, Craig B Wilen, Jianbin Wang, Jennifer Duong, Anthony J Secreto, Gwenn A Danet-Desnoyers, James L Riley, Phillip D Gregory, Carl H June, Michael C Holmes and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
8.4field-weighted citation impact, top 2% 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

78 citing papers in PubMed, 160 citations in OpenAlex.

  1. Review
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  5. Article
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  9. Review
  10. Review
  11. Review
  12. Review
  13. Gene editing and its applications in biomedicine.Science China. Life sciences · 2022
    Review
  14. Article
  15. Article
  16. Article
  17. Highly efficient CD4+ T cell targeting and genetic recombination using engineered CD4+ cell-homing mRNA-LNPs.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  18. Review
  19. Review
  20. CRISPR/Cas-Dependent and Nuclease-FreeHuman gene therapy · 2021
    Review

18 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 at 3 institutions in 1 country.

Chuka A DidiguDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA;
Craig B Wilen
Jianbin Wang
Jennifer Duong
Anthony J Secreto
Gwenn A Danet-Desnoyers
James L Riley
Phillip D Gregory
Carl H June
Michael C Holmes
Robert W Doms
University of Pennsylvania · USSangamo BioSciences (United States) · USCancer Research Institute · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6M
Sequencing and Viral Evolution CoreU19AI082628 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI RILEY, JAMES L. · 2009 to 2013
$8.9M
NCI NIH HHS P30 CA016520NIAID NIH HHS P30 AI045008NIAID NIH HHS U19 AI082628
6 · The paper itself

Abstract

HIV-1 entry into CD4(+) T cells requires binding of the virus to CD4 followed by engagement of either the C-C chemokine receptor 5 (CCR5) or C-X-C chemokine receptor 4 (CXCR4) coreceptor. Pharmacologic blockade or genetic inactivation of either coreceptor protects cells from infection by viruses that exclusively use the targeted coreceptor. We have used zinc-finger nucleases to drive the simultaneous genetic modification of both ccr5 and cxcr4 in primary human CD4(+) T cells. These gene-modified cells proliferated normally and were resistant to both CCR5- and CXCR4-using HIV-1 in vitro. When introduced into a humanized mouse model of HIV-1 infection, these coreceptor negative cells engraft and traffic normally, and are protected from infection with CCR5- and CXCR4-using HIV-1 strains. These data suggest that simultaneous disruption of the HIV coreceptors may provide a useful approach for the long-term, drug-free treatment of established HIV-1 infections.

Indexed as

Zinc FingersAnimalsCD4-Positive T-LymphocytesCell ProliferationEndodeoxyribonucleasesFemaleHEK293 CellsHIV-1HIV InfectionsHumansMaleMiceReceptors, CCR5Receptors, ChemokineReceptors, CXCR4CCR5 protein, humanCXCR4 protein, humanEndodeoxyribonucleasesReceptors, CCR5Receptors, ChemokineReceptors, CXCR4

Identifiers

PMID24162716
PMCPMC3879906
OpenAlexW2020977401

What OpenQuestion holds

Textmetadata
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.