Evidence map›Paper›PMID 25689223›Full record

ArticleMolecular therapy. Nucleic acids2015

RNAi-Mediated CCR5 Knockdown Provides HIV-1 Resistance to Memory T Cells in Humanized BLT Mice.

Saki Shimizu, Gene-Errol Ringpis, Matthew D Marsden, Ruth V Cortado, Holly M Wilhalme, David Elashoff, Jerome A Zack, Irvin S Y Chen, Dong Sung An

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Nucleic acids, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.0field-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

23 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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  8. Humanized Mice as a Tool to Study Sepsis-More Than Meets the Eye.International journal of molecular sciences · 2021
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Stem cell-based therapies for HIV/AIDS.Advanced drug delivery reviews · 2016
    Review
  18. Review
  19. Article
  20. In vivo platforms for analysis of HIV persistence and eradication.The Journal of clinical investigation · 2016
    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

9 authors at 2 institutions in 1 country.

Saki Shimizu1] Hematology-Oncology, the Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA [2] School of Nursing, University of California, Los Angeles, California, USA [3] UCLA AIDS Institute, Los Angeles, California, USA.
Gene-Errol Ringpis1] Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA [2] UCLA AIDS Institute, Los Angeles, California, USA.
Matthew D Marsden1] Hematology-Oncology, the Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA [2] UCLA AIDS Institute, Los Angeles, California, USA.
Ruth V Cortado1] School of Nursing, University of California, Los Angeles, California, USA [2] UCLA AIDS Institute, Los Angeles, California, USA.
Holly M WilhalmeDepartment of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
David ElashoffDepartment of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Jerome A Zack1] Hematology-Oncology, the Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA [2] Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA [3] UCLA AIDS Institute, Los Angeles, California, USA.
Irvin S Y Chen1] Hematology-Oncology, the Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA [2] Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA [3] UCLA AIDS Institute, Los Angeles, California, USA.
Dong Sung An1] Hematology-Oncology, the Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA [2] School of Nursing, University of California, Los Angeles, California, USA [3] UCLA AIDS Institute, Los Angeles, California, USA.
University of California, Los Angeles · USBlack AIDS Institute · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KITCHEN, SCOTT G · 1991 to 2018
$39.9M
Using NK Cells to eliminate the latent HIV reservoirU19AI096113 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MARGOLIS, DAVID M. · 2011 to 2015
$39.5M
Genetic protection of hematopoietic stem cells for stable HIV controlR01AI100652 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AN, DONG SUNG · 2012 to 2016
$1.9M
Investigate stability RNA interference human lymphocytesR01HL086409 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AN, DONG SUNG · 2006 to 2009
$1.6M
NCATS NIH HHS UL1 TR000124NHLBI NIH HHS R01 HL086409NIAID NIH HHS N01 AI070010NIAID NIH HHS P30 AI028697NIAID NIH HHS R01 AI100652NIAID NIH HHS U19 AI096113
6 · The paper itself

Abstract

Transplantation of hematopoietic stem/progenitor cells (HSPC) modified with a lentiviral vector bearing a potent nontoxic short hairpin RNA (sh1005) directed to the HIV coreceptor CCR5 is capable of continuously producing CCR5 downregulated CD4+ T lymphocytes. Here, we characterized HIV-1 resistance of the sh1005-modified CD4+ T lymphocytes in vivo in humanized bone marrow/liver/thymus (hu BLT) mice. The sh1005-modified CD4+ T lymphocytes were positively selected in CCR5-tropic HIV-1-challenged mice. The sh1005-modified memory CD4+ T lymphocytes (the primary target of CCR5-tropic HIV-1) expressing sh1005 were maintained in lymphoid tissues in CCR5-tropic HIV-1-challenged mice. Frequencies of HIV-1 p24 expressing cells were significantly reduced in the sh1005-modified splenocytes by ex vivo cell stimulation confirming that CCR5 downregulated sh1005 modified cells are protected from viral infection. These results demonstrate that stable CCR5 downregulation through genetic modification of human HSPC by lentivirally delivered sh1005 is highly effective in providing HIV-1 resistance. Our results provide in vivo evidence in a relevant small animal model that sh1005 is a potent early-step anti-HIV reagent that has potential as a novel anti-HIV-1 HSPC gene therapeutic reagent for human applications.

Identifiers

PMID25689223
PMCPMC4345313
OpenAlexW2064377018

What OpenQuestion holds

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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.