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PMID: 16428288 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Foamy virus vector integration sites in normal human cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 5 ·2006-01-31 ·Pages 1498-503

Trobridge GD, Miller DG, Jacobs MA, Allen JM, Kiem HP, Kaul R, Russell DW

Abstract

Foamy viruses (FVs) or spumaviruses are retroviruses that have been developed as vectors, but their integration patterns have not been described. We have performed a large-scale analysis of FV integration sites in unselected human fibroblasts (n = 1,008) and human CD34(+) hematopoietic cells (n = 1,821) by using a bacterial shuttle vector and a comparable analysis of lentiviral vector integration sites in CD34(+) cells (n = 1,331). FV vectors had a distinct integration profile relative to other types of retroviruses. They did not integrate preferentially within genes, despite a modest preference for integration near transcription start sites and a significant preference for CpG islands. The genomewide distribution of FV vector proviruses was nonrandom, with both clusters and gaps. Transcriptional profiling showed that gene expression had little influence on integration site selection. Our findings suggest that FV vectors may have desirable integration properties for gene therapy applications.

MeSH Terms
Antigens, CD34/biosynthesis,metabolism Cell Line CpG Islands DNA/metabolism Fibroblasts/metabolism Gene Expression Regulation Genetic Therapy/methods Genetic Vectors/metabolism Genome Green Fluorescent Proteins/metabolism Hematopoietic Stem Cells/cytology Humans Models, Genetic Models, Statistical Mutagenesis Oligonucleotide Array Sequence Analysis Proviruses/genetics Retroviridae/genetics Spumavirus/genetics Transcription, Genetic Virus Integration
Chemicals
Antigens, CD34 Green Fluorescent Proteins DNA
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Trobridge Grant D
Department of Medicine, Division of Hematology, University of Washington, Seattle, WA 98195, USA.
Miller Daniel G
Jacobs Michael A
Allen James M
Kiem Hans-Peter
Kaul Rajinder
Russell David W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0510046103
Published
2006-01-31
Epub
2006-00-20
Pages
1498-503
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1360565
Subset
IM
Grants
NIDDK NIH HHS · K08 DK062100 · United States
External Links
PubMed source DOI: 10.1073/pnas.0510046103 PMC Full Text View journal details
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