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Short-term cytotoxic effects and long-term instability of RNAi delivered using lentiviral vectors

Published in BMC molecular biology. 2004, vol. 5, 9
Abstract RNA interference (RNAi) can potently reduce target gene expression in mammalian cells and is in wide use for loss-of-function studies. Several recent reports have demonstrated that short double-stranded RNAs (dsRNAs), used to mediate RNAi, can also induce an interferon-based response resulting in changes in the expression of many interferon-responsive genes. Off-target gene silencing has also been described, bringing into question the validity of certain RNAi-based approaches for studying gene function. We have targeted the plasminogen activator inhibitor-2 (PAI-2 or SERPINB2) mRNA using lentiviral vectors for delivery of U6 promoter-driven PAI-2-targeted short hairpin RNA (shRNA) expression. PAI-2 is reported to have anti-apoptotic activity, thus reduction of endogenous expression may be expected to make cells more sensitive to programmed cell death.
Keywords 2',5'-Oligoadenylate Synthetase/geneticsBiological Markers/metabolismCell LineCell Line, TumorDrug Delivery Systems/methodsEnzyme Induction/geneticsGene Expression/geneticsGene SilencingGene Transfer TechniquesGenetic Vectors/geneticsHeLa Cells/drug effectsHumansKidney/cytology/drug effects/embryologyLentivirus/genetics/metabolismPlasminogen Activator Inhibitor 2/biosynthesis/genetics/metabolismRNA StabilityRNA, Antisense/administration & dosage/adverse effects/metabolismRNA, Messenger/genetics/metabolismRNA, Small Interfering/adverse effects/biosynthesis/metabolismTransduction, Genetic/methods
PMID: 15291968
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FISH, Richard, KRUITHOF, Egbert. Short-term cytotoxic effects and long-term instability of RNAi delivered using lentiviral vectors. In: BMC molecular biology, 2004, vol. 5, p. 9. doi: 10.1186/1471-2199-5-9 https://archive-ouverte.unige.ch/unige:36194

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Deposited on : 2014-04-29

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