Characterization of novel safe lentiviral vectors derived from simian immunodeficiency virus (SIVmac251) that efficiently transduce mature human dendritic cells
| Autor: | S Blanchard, Pierre-Olivier Vidalain, Arend Jan Winter, Philippe Leissner, François-Loïc Cosset, Jean-Luc Darlix, Didier Nègre, Chantal Rabourdin-Combe, Majid Mehtali, Ghislaine Duisit, Philippe Moullier, Philippe E. Mangeot |
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| Rok vydání: | 2000 |
| Předmět: |
Virosomes
viruses Genetic Vectors Green Fluorescent Proteins Gene Expression Biology Transfection medicine.disease_cause Recombinant virus Cell Line Transduction (genetics) Multiplicity of infection Genetics medicine Animals Humans Molecular Biology Reporter gene Genetic transfer virus diseases Dendritic Cells Dendritic cell Simian immunodeficiency virus biology.organism_classification Virology Luminescent Proteins Lentivirus HIV-1 Molecular Medicine Simian Immunodeficiency Virus Genetic Engineering |
| Zdroj: | Gene Therapy. 7:1613-1623 |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/sj.gt.3301292 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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