Evidence map›Paper›PMID 20018916›Full record

ArticleBlood2010

A highly efficient short hairpin RNA potently down-regulates CCR5 expression in systemic lymphoid organs in the hu-BLT mouse model.

Saki Shimizu, Patrick Hong, Balamurugan Arumugam, Lauren Pokomo, Joshua Boyer, Naoya Koizumi, Panyamol Kittipongdaja, Angela Chen, Greg Bristol, Zoran Galic and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

106 citing papers in PubMed, 150 citations in OpenAlex.

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  19. Engineering CAR T Cells to Target the HIV Reservoir.Frontiers in cellular and infection microbiology · 2020
    Review
  20. Article

46 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

15 authors at 2 institutions in 1 country.

Saki ShimizuDepartment of Medicine, Division of Hematology-Oncology, UCLA AIDS Institute, David Geffen School of Medicine, University of California-Los Angeles, 615 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
Patrick Hong
Balamurugan Arumugam
Lauren Pokomo
Joshua Boyer
Naoya Koizumi
Panyamol Kittipongdaja
Angela Chen
Greg Bristol
Zoran Galic
Jerome A Zack
Otto Yang
Irvin S Y Chen
Benhur Lee
Dong Sung An
Black AIDS Institute · USUniversity of California, Los Angeles · US

Funding

Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTON, PETER A · 1991 to 2018
$39.9M
Transductionally Redirected /Transcriptionally RestricteP50CA086306 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HERSCHMAN, HARVEY R. · 2000 to 2014
$29.0M
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
Academic Training in RheumatologyT32AR053463 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SINGH, RAM RAJ · 2007 to 2011
$1.1M
NCI NIH HHS CA 086306NCI NIH HHS P50 CA086306NHLBI NIH HHS 1R01 HL 086409NHLBI NIH HHS R01 HL086409NIAID NIH HHS AI 028697NIAID NIH HHS P30 AI028697NIAID NIH HHS R01 AI100652NIAMS NIH HHS T32 AR 053463NIAMS NIH HHS T32 AR053463
6 · The paper itself

Abstract

Inhibiting the expression of the HIV-1 coreceptor CCR5 holds great promise for controlling HIV-1 infection in patients. Here we report stable knockdown of human CCR5 by a short hairpin RNA (shRNA) in a humanized bone marrow/liver/thymus (BLT) mouse model. We delivered a potent shRNA against CCR5 into human fetal liver-derived CD34(+) hematopoietic progenitor/stem cells (HPSCs) by lentiviral vector transduction. We transplanted vector-transduced HPSCs solidified with Matrigel and a thymus segment under the mouse kidney capsule. Vector-transduced autologous CD34(+) cells were subsequently injected in the irradiated mouse, intended to create systemic reconstitution. CCR5 expression was down-regulated in human T cells and monocytes/macrophages in systemic lymphoid tissues, including gut-associated lymphoid tissue, the major site of HIV-1 replication. The shRNA-mediated CCR5 knockdown had no apparent adverse effects on T-cell development as assessed by polyclonal T-cell receptor Vbeta family development and naive/memory T-cell differentiation. CCR5 knockdown in the secondary transplanted mice suggested the potential of long-term hematopoietic reconstitution by the shRNA-transduced HPSCs. CCR5 tropic HIV-1 infection was effectively inhibited in mouse-derived human splenocytes ex vivo. These results demonstrate that lentiviral vector delivery of shRNA into human HPSCs could stably down-regulate CCR5 in systemic lymphoid organs in vivo.

Indexed as

Hematopoietic Stem Cell TransplantationHIV-1AnimalsBone MarrowCell DifferentiationDisease Models, AnimalDown-RegulationGene Knockdown TechniquesHematopoietic Stem CellsHIV InfectionsHumansImmunologic MemoryLentivirusLiverMiceMice, Inbred NODReceptors, Antigen, T-Cell, alpha-betaReceptors, CCR5

Identifiers

PMID20018916
PMCPMC2830759
OpenAlexW1982047006

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.