Evidence map›Paper›PMID 21533216›Full record

ArticlePLoS pathogens2011

Engineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc-finger nucleases.

Craig B Wilen, Jianbin Wang, John C Tilton, Jeffrey C Miller, Kenneth A Kim, Edward J Rebar, Scott A Sherrill-Mix, Sean C Patro, Anthony J Secreto, Andrea P O Jordan and 13 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
6.6field-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

91 citing papers in PubMed, 140 citations in OpenAlex.

  1. Trial
  2. Searching for a HIV-1 Cure.Theranostics · 2026
    Review
  3. Review
  4. Article
  5. Review
  6. Precise excision of HTLV-1 provirus with a designer-recombinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  7. HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022
    Review
  8. Therapeutic potentials of CRISPR-Cas genome editing technology in human viral infections.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. HIV-Resistant and HIV-Specific CAR-Modified CD4Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Article
  16. Review
  17. Article
  18. Application of CRISPR/Cas9-Based Gene Editing in HIV-1/AIDS Therapy.Frontiers in cellular and infection microbiology · 2019
    Review
  19. Review
  20. Article

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

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

23 authors at 3 institutions in 1 country.

Craig B WilenDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
Jianbin Wang
John C Tilton
Jeffrey C Miller
Kenneth A Kim
Edward J Rebar
Scott A Sherrill-Mix
Sean C Patro
Anthony J Secreto
Andrea P O Jordan
Gary Lee
Joshua Kahn
Pyone P Aye
Bruce A Bunnell
Andrew A Lackner
James A Hoxie
Gwenn A Danet-Desnoyers
Frederic D Bushman
James L Riley
Philip D Gregory
Carl H June
Michael C Holmes
Robert W Doms
University of Pennsylvania · USSangamo BioSciences (United States) · USTulane University · US

Funding

ZCM:A NOVEL BROAD-SPECTRUM MICROBICIDE FOR SEXUALLY TRANSMITTED INFECTIONSP51RR000164 · NCRR · TULANE UNIVERSITY OF LOUISIANA · PI VEAZEY, RONALD S. · 1985 to 2011
$100.1M
Molecular Virology and Systems Biology Screening CoreP01AI090935 · NIAID · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI CHANDA, SUMIT K · 2010 to 2014
$20.4M
Sequencing and Viral Evolution CoreU19AI082628 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI RILEY, JAMES L. · 2009 to 2013
$8.9M
HIV entry and its inhibitionR01AI040880 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DOMS, ROBERT W. · 1997 to 2010
$4.2M
Mechanisms of HIV Resistance to CCR5 Inhibitors and Consequences for PathogenesisF32AI077370 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI TILTON, JOHN CHRISTIAN · 2008 to 2010
$163k
NCRR NIH HHS P51 RR000164NIAID NIH HHS F32 1F32AI077370NIAID NIH HHS F32 AI077370NIAID NIH HHS P01 AI090935NIAID NIH HHS R01 AI 040880NIAID NIH HHS R01 AI040880NIAID NIH HHS T32 AI000632NIAID NIH HHS U19 AI082628
6 · The paper itself

Abstract

HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells. Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic (R5) virus strains. As an approach to inactivating CCR5, we introduced CCR5-specific zinc-finger nucleases into human CD4+ T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4) in place of or in addition to CCR5 (R5X4) remains. Here we describe engineering a pair of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error-prone non-homologous DNA end-joining. The resulting cells proliferated normally and were resistant to infection by X4-tropic HIV-1 strains. CXCR4 could also be inactivated in ccr5Δ32 CD4+ T cells, and we show that such cells were resistant to all strains of HIV-1 tested. Loss of CXCR4 also provided protection from X4 HIV-1 in a humanized mouse model, though this protection was lost over time due to the emergence of R5-tropic viral mutants. These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals.

Indexed as

AnimalsCD4-Positive T-LymphocytesCell ProliferationDeoxyribonucleasesDisease Models, AnimalGenetic EngineeringHIV-1HIV InfectionsHumansMacaca mulattaMiceReceptors, CCR5Receptors, CXCR4Transplantation, AutologousTransplantation, HeterologousVirus InternalizationCXCR4 protein, humanDeoxyribonucleasesReceptors, CCR5Receptors, CXCR4

Identifiers

PMID21533216
PMCPMC3077364
OpenAlexW2007764764

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.