Abstract
We describe the generation and the characterization of new lentiviral vectors derived from SIVmac251, a simian immunodeficiency virus (SIV). A methodical approach was used to engineer both efficient and safe packaging constructs allowing the production of SIV viral core proteins. SIV-vectors encoding GFP (green fluorescent protein) were generated as VSV-G-pseudotyped particles upon transient expression of the vector construct and helper functions in 293 cells. The SIV vectors were able to transduce efficiently various target cell types at low multiplicity of infection, including monocyte-differentiated human dendritic cells (DCs) which retained their capacity to differentiate into mature DCs after gene transfer. Transduction of the DCs by the SIV vectors was prevented when infections were performed in the presence of AZT, a reverse-transcriptase inhibitor. After gene transfer, expression of the GFP in the target cells remained constant after several weeks, indicating that the vectors had been stably integrated into the genome of the host cells. Preparations of SIV vectors were systematically checked for the absence of replication-competent and recombinant retroviruses but remained negative, suggesting the innocuousness of these novel gene delivery vectors. Side-to-side comparisons with vectors derived from HIV-1 (human immunodeficiency virus) indicated that the SIV vectors were equally potent in transducing proliferating target cells. Finally, we have determined the infectivity of SIV vectors pseudotyped with surface glycoproteins of several membrane-enveloped viruses.
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Acknowledgements
We thank J Mullins for the SIVmac251 molecular clone, Didier Trono and Romain Zufferey for the HIV-1 vector and helper plasmids, Transgene SA for the MLV vector and helper plasmids, and the Schering-Plough Laboratory for Immunological Research for the CD40 ligand-expressing cells. We thank Bertrand Boson for helpful discussions and Roger Legrand for providing the SIVmac251 viral stock. This work was supported by Institut National de la Santé et de la Recherche Médicale (INSERM), Agence Nationale pour la Recherche contre le SIDA (ANRS), Association Française contre les Myopathies (AFM), Association pour la Recherche contre le Cancer (ARC), Mutuelle Générale de l'Enseignement National (MGEN), and the European Community (EC).
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Nègre, D., Mangeot, PE., Duisit, G. et al. Characterization of novel safe lentiviral vectors derived from simian immunodeficiency virus (SIVmac251) that efficiently transduce mature human dendritic cells. Gene Ther 7, 1613–1623 (2000). https://doi.org/10.1038/sj.gt.3301292
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DOI: https://doi.org/10.1038/sj.gt.3301292
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