Kinetics and characteristics of replication-competent revertants derived from self-inactivating foamy virus vectors.

Abstract:

:In this study, self-inactivating (SIN) retroviral vectors based on feline foamy virus (FFV) were constructed and analysed. The FFV SIN vectors were devoid of the core FFV long terminal repeat promoter plus upstream sequences but contained all structural and regulatory genes. This design allowed sensitive detection of replication-competent revertants (RCRs). The FFV SIN vectors efficiently transduced the green fluorescence protein into recipient cells. However, RCRs appeared after serial passages of transduced cells. In all RCR clones analysed, parts of the heterologous cytomegalovirus immediate early promoter, originally driving expression of the FFV vector genome, were taken up to restore the deleted SIN promoter function required for replication competence. The RCRs were strongly reduced in replication capacity compared with the parental replication-competent vectors containing the FFV promoter. In all RCR genomes analysed, the uptake of the heterologous promoter was accompanied by deletion of almost the complete marker gene. Although the RCRs described in this study may not have the capacity to spread in humans and animals, they may pose a theoretical risk, for instance during transduction of haematopoietic stem cells. Thus, FV-based SIN vectors require additional genetic modifications in order to avoid RCRs.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Bastone P,Löchelt M

doi

10.1038/sj.gt.3302185

keywords:

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

465-73

issue

5

eissn

0969-7128

issn

1476-5462

pii

3302185

journal_volume

11

pub_type

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