Integration site selection by HIV-based vectors in dividing and growth-arrested IMR-90 lung fibroblasts

Details

Serval ID
serval:BIB_B3C6DE07DCAB
Type
Article: article from journal or magazin.
Collection
Publications
Title
Integration site selection by HIV-based vectors in dividing and growth-arrested IMR-90 lung fibroblasts
Journal
Molecular Therapy
Author(s)
Ciuffi  A., Mitchell  R. S., Hoffmann  C., Leipzig  J., Shinn  P., Ecker  J. R., Bushman  F. D.
ISSN
1525-0016
Publication state
Published
Issued date
02/2006
Peer-reviewed
Oui
Volume
13
Number
2
Pages
366-73
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Feb
Abstract
DNA integration is a defining step in the retroviral life cycle and the basis of stable gene transfer in retrovirus-based gene therapy. Previous studies of integration by HIV-based vectors have shown that integration is not random, but favored in active transcription units. Studies to date have focused on HIV integration in dividing cells, leaving open the question of whether integration target site selection might differ in nondividing cells. According to one idea, division of the host cell might be required for favored integration in transcription units, possibly as a result of chromatin remodeling during DNA replication. Here we have investigated this issue by comparing integration in dividing IMR-90 primary lung fibroblasts to integration in nondividing IMR-90 cells arrested in G1 by serum starvation and contact inhibition. We identified several differences in integration site selection in arrested versus dividing cells, including the frequency of integration in transcription units and in gene-rich regions. However, integration in nondividing cells was in fact more favored in transcription units, contrary to the idea that cell division was important for this bias. These data provide the first view of lentiviral integration in nondividing cells and help constrain models for the mechanism of favored integration in genes.
Pubmed
Web of science
Open Access
Yes
Create date
22/02/2008 14:45
Last modification date
20/08/2019 15:22
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