Evidence map›Paper›PMID 23388702›Full record

ArticleGene therapy2013

Lack of genotoxicity due to foamy virus vector integration in human iPSCs.

D R Deyle, I F Khan, G Ren, D W Russell

Abstract read
In one paragraph

Article in Gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Evolving Gene Therapy in Primary Immunodeficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2017
    Review
  6. Insulated Foamy Viral Vectors.Human gene therapy · 2016
    Article
  7. Review
  8. Article
  9. 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

4 authors.

D R DeyleDepartments of Medicine, University of Washington, Seattle, WA 98195, USA.
I F Khan
G Ren
D W Russell

Funding

VECTOR CONSTRUCTIONS FOR GENE THERAPY OF SICKLE CELL DISEASEP01HL053750 · NHLBI · UNIVERSITY OF WASHINGTON · PI RIVIERI, ISABELLE · 1994 to 2014
$30.4M
GENE TARGETING BY VIRAL VECTORSR01DK055759 · NIDDK · UNIVERSITY OF WASHINGTON · PI RUSSELL, DAVID W · 1999 to 2017
$5.8M
Treatment of Leukocyte Adhesion Deficiency by Foamy Virus VectorsR01HL085107 · NHLBI · UNIVERSITY OF WASHINGTON · PI RUSSELL, DAVID W · 2006 to 2016
$4.2M
GENE TARGETING STRATEGIES FOR THE TREATMENT OF OSTEOGENESIS IMPERFECTAR01AR048328 · NIAMS · UNIVERSITY OF WASHINGTON · PI RUSSELL, DAVID W · 2001 to 2010
$4.0M
Gene targeting with AAV vectors for the treatment of Osteogenesis ImperfectaK08AR053917 · NIAMS · UNIVERSITY OF WASHINGTON · PI DEYLE, DAVID R · 2008 to 2012
$658k
Derivation and Transplantation of Histocompatible Pluripotent Stem CellsR01GM086497 · NIGMS · UNIVERSITY OF WASHINGTON · PI RUSSELL, DAVID W · 2009 to 2010
$624k
NHLBI NIH HHS HL53750NHLBI NIH HHS P01 HL053750NHLBI NIH HHS R01 HL085107NIAMS NIH HHS AR48328NIAMS NIH HHS AR48328-09S1NIAMS NIH HHS AR53917NIAMS NIH HHS K08 AR053917NIAMS NIH HHS R01 AR048328NIDDK NIH HHS DK55759NIDDK NIH HHS R01 DK055759NIGMS NIH HHS GM86497NIGMS NIH HHS R01 GM086497
6 · The paper itself

Abstract

Integrating vectors can lead to the dysregulation of nearby chromosomal genes, with important consequences for clinical trials and cellular engineering. This includes the retroviral and lentiviral vectors commonly used for deriving induced pluripotent stem cells (iPSCs). We previously used integrating foamy virus (FV) vectors expressing OCT4, SOX2, MYC and KLF4 to reprogram osteogenesis imperfecta mesenchymal stem cells (MSCs). Here, we have studied the effects of 10 FV vector proviruses on neighboring gene expression in four iPSC lines and their corresponding iPSC-derived MSC (iMSCs). Gene expression profiles in these iPSC lines showed that none of the 38 genes within 300 kb up- or downstream of integrated proviruses had a significant difference in mRNA levels, including five genes with proviruses in their transcription units. In the iMSCs derived from these iPSCs, the same type of analysis showed a single dysregulated transcript out of 46 genes found near proviruses. This frequency of dysregulation was similar to that of genes lacking nearby proviruses, so it may have been due to interclonal variation and/or measurement inaccuracies. While the number of integration sites examined in this paper is limited, our results suggest that integrated FV proviruses do not impact the expression of chromosomal genes in pluripotent human stem cells or their differentiated derivatives. This interpretation is consistent with previous reports that FV vectors have minimal genotoxicity, even when integrating near or within genes.

Indexed as

Genetic VectorsCell DifferentiationCell LineGene Expression Regulation, DevelopmentalHumansInduced Pluripotent Stem CellsKruppel-Like Factor 4SpumavirusVirus IntegrationKruppel-Like Factor 4

Identifiers

PMID23388702
PMCPMC3655141

What OpenQuestion holds

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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.