Evidence map›Paper›PMID 18587011›Full record

ArticleBlood2008

Interfering RNA-mediated purine analog resistance for in vitro and in vivo cell selection.

Christopher C Porter, James DeGregori

Open access · greenAbstract readEvaluation Study
In one paragraph

Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Review
  3. A Multidrug-resistant Engineered CAR T Cell for Allogeneic Combination Immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2015
    Article
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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

2 authors at 2 institutions in 1 country.

Christopher C PorterRick Wilson Center for Cancer and Blood Disorders, The Children's Hospital, Aurora, CO, USA. James.DeGregori@UCHSC.edu
James DeGregori
Center for Cancer and Blood Disorders · USUniversity of Colorado Denver · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
POSTGRADUATE TRAINING IN PEDIATRIC ONCOLOGYT32CA082086 · NCI · UNIVERSITY OF COLORADO DENVER · PI GORE, LIA · 2000 to 2015
$4.1M
Poor competition in hematopoietic stem/progenitor pools favors tumorigenesisR01CA109657 · NCI · UNIVERSITY OF COLORADO DENVER · PI DEGREGORI, JAMES V · 2005 to 2009
$1.1M
Testing the safety and efficacy of inhibitory RNA mediated purine analog resistanR21HL094921 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI PORTER, CHRISTOPHER C · 2009 to 2010
$541k
NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA109657NCI NIH HHS T32 CA082086NHLBI NIH HHS R21 HL094921
6 · The paper itself

Abstract

The advancement of gene therapy has been slowed, in part, by inefficient transduction of targeted cells and poor long-term engraftment of genetically modified cells. Thus, the ability to select for a desired population of cells within a recipient would be of great benefit for improving gene therapy. Proposed strategies for in vivo cell selection using drug resistance genes have had disappointing outcomes and/or require highly genotoxic medications to be effective. We hypothesized that resistance to purine analogs, a well-tolerated, relatively low-toxicity class of medications, could be provided to cells using interfering RNA against hypoxanthine phosphoribosyl transferase. Using a lentiviral vector, we found that interfering RNA-mediated purine analog resistance (iPAR) provided relative resistance to 6-thioguanine (6TG) in murine hematopoietic cells compared with control- and untransduced cells. iPAR attenuated 6TG-induced G(2)/M checkpoint activation, cell-cycle arrest, and apoptosis. Furthermore, in recipients of transplanted bone marrow cells with iPAR, treatment with 6TG resulted in increased percentages of transduced peripheral blood cells and hematopoietic progenitor cells in the bone marrow. Secondary transplantations resulted in higher hematopoietic contributions from 6TG-treated primary recipients relative to phosphate-buffered saline-treated recipients. These findings indicate that iPAR/6TG can be used for in vivo hematopoietic progenitor cell selection.

Indexed as

AnimalsApoptosisCell CycleCells, CulturedCell SeparationDrug ResistanceGene Knockdown TechniquesGenetic VectorsHematopoietic Stem CellsHumansHypoxanthine PhosphoribosyltransferaseLentivirusMiceMice, Inbred C57BLPurinesRNA, Small InterferingHypoxanthine PhosphoribosyltransferasePurinesRNA, Small InterferingThioguanine

Identifiers

PMID18587011
PMCPMC2597122
OpenAlexW2002954014

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.