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

Gene Therapy volume 11, pages 465–473 (2004)Cite this article

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.

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Acknowledgements

We thank Jennifer Reed, Jürgen Kleinschmidt, Nadine Kirchner (DKFZ), and Allison German (Bristol University, UK) for critically reading the manuscript, and Harald zur Hausen for continuous support.

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  1. Abt. Genomveränderung und Carcinogenese, Forschungsschwerpunkt Infektion und Krebs, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    P Bastone & M Löchelt

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Bastone, P., Löchelt, M. Kinetics and characteristics of replication-competent revertants derived from self-inactivating foamy virus vectors. Gene Ther 11, 465–473 (2004). https://doi.org/10.1038/sj.gt.3302185

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