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dc.contributor.authorHølvold, Linn Benjaminsen
dc.contributor.authorFredriksen, Børge Nilsen
dc.contributor.authorBøgwald, Jarl
dc.contributor.authorDalmo, Roy Ambli
dc.date.accessioned2014-03-19T09:21:59Z
dc.date.available2014-03-19T09:21:59Z
dc.date.issued2013
dc.description.abstractThe use of poly-(D,L-lactic-co-glycolic) acid (PLGA) particles as carriers for DNA delivery has received considerable attention in mammalian studies. DNA vaccination of fish has been shown to elicit durable transgene expression, but no reports exist on intramuscular administration of PLGA-encapsulated plasmid DNA (pDNA). We injected Atlantic salmon (Salmo salar L.) intramuscularly with a plasmid vector containing a luciferase (Photinus pyralis) reporter gene as a) naked pDNA, b) encapsulated into PLGA nano- (∼320 nm) (NP) or microparticles (∼4 μm) (MP), c) in an oil-based formulation, or with empty particles of both sizes. The ability of the different pDNA-treatments to induce transgene expression was analyzed through a 70-day experimental period. Anatomical distribution patterns and depot effects were determined by tracking isotope labeled pDNA. Muscle, head kidney and spleen from all treatment groups were analyzed for proinflammatory cytokines (TNF-α, IL-1β), antiviral genes (IFN-α, Mx) and cytotoxic T-cell markers (CD8, Eomes) at mRNA transcription levels at days 1, 2, 4 and 7. Histopathological examinations were performed on injection site samples from days 2, 7 and 30. Injection of either naked pDNA or the oil-formulation was superior to particle treatments for inducing transgene expression at early time-points. Empty particles of both sizes were able to induce proinflammatory immune responses as well as degenerative and inflammatory pathology at the injection site. Microparticles demonstrated injection site depots and an inflammatory pathology comparable to the oil-based formulation. In comparison, the distribution of NP-encapsulated pDNA resembled that of naked pDNA, although encapsulation into NPs significantly elevated the expression of antiviral genes in all tissues. Together the results indicate that while naked pDNA is most efficient for inducing transgene expression, the encapsulation of pDNA into NPs up-regulates antiviral responses that could be of benefit to DNA vaccination.en
dc.identifier.citationFish and Shellfish Immunology 35(2013) nr. 3 s. 890-899en
dc.identifier.cristinIDFRIDAID 1072762
dc.identifier.doihttp://dx.doi.org/10.1016/j.fsi.2013.06.030
dc.identifier.issn1050-4648
dc.identifier.urihttps://hdl.handle.net/10037/5966
dc.identifier.urnURN:NBN:no-uit_munin_5654
dc.language.isoengen
dc.publisherElsevieren
dc.rights.accessRightsopenAccess
dc.subjectVDP::Mathematics and natural science: 400::Basic biosciences: 470::Genetics and genomics: 474en
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Genetikk og genomikk: 474en
dc.titleTransgene and immune gene expression following intramuscular injection of Atlantic salmon (Salmo salar L.) with DNA-releasing PLGA nano- and microparticlesen
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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