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Molecular Therapy
Article . 2006 . Peer-reviewed
License: CC BY NC ND
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Molecular Therapy
Article
License: CC BY NC ND
Data sources: UnpayWall
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Molecular Therapy
Article . 2006
License: CC BY NC ND
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Integration Bias of Gammaretrovirus Vectors following Transduction and Growth of Primary Mouse Hematopoietic Progenitor Cells with and without Selection

Authors: Aker, Mari; Tubb, Julie; Miller, Daniel G.; Stamatoyannopoulos, George; Emery, David W.;

Integration Bias of Gammaretrovirus Vectors following Transduction and Growth of Primary Mouse Hematopoietic Progenitor Cells with and without Selection

Abstract

The recent recognition that recombinant retrovirus vectors can induce oncogenic transformation has stimulated much interest in the pattern of vector integration sites. We report here on the integration pattern of a gammaretrovirus reporter vector following transduction and ex vivo culture of primary mouse bone marrow progenitor cells in the absence and presence of drug selection. Using a novel method of cloning junction fragments, we observed no bias for integrations within genes, but did observe a bias for integrations within gene-dense regions and especially near transcriptional start sites of highly active genes, similar to previous reports in other cell types. We also document a novel bias for integrations within or near a class of genes that encode nuclear-localized proteins. We found that drug selection resulted in an increase in the frequency of recovered integration events that were located within the beginning of genes, integration events that were located in less gene-dense regions, and integration events that were oriented in an antisense direction relative to flanking gene transcription. Taken together, these studies provide new insights into the nature of retrovirus vector integration patterns in primary cells and demonstrate that selection based on vector expression can bias the integration site repertoire.

Related Organizations
Keywords

Pharmacology, Virus Integration, Genetic Vectors, Neomycin, Hematopoietic Stem Cells, Mice, Transduction, Genetic, Drug Discovery, Genetics, Molecular Medicine, Animals, Female, Cloning, Molecular, Gammaretrovirus, Transcription Initiation Site, Molecular Biology

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    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
13
Average
Average
Top 10%
hybrid