Evaluation of canonical siRNA and dicer substrate RNA for inhibition of hepatitis C virus genome replication: a comparative study

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dc.contributor.authorCarneiro, Bruno [UNESP]
dc.contributor.authorSilva Braga, Ana Claudia [UNESP]
dc.contributor.authorBatista, Mariana Nogueira [UNESP]
dc.contributor.authorHarris, Mark
dc.contributor.authorRahal, Paula [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniv Leeds
dc.date.accessioned2015-10-21T21:22:30Z
dc.date.available2015-10-21T21:22:30Z
dc.date.issued2015-02-23
dc.description.abstractHepatitis C virus (HCV) frequently establishes persistent infections in the liver, leading to the development of chronic hepatitis and, potentially, to liver cirrhosis and hepatocellular carcinoma at later stages. The objective of this study was to test the ability of five Dicer substrate siRNAs (DsiRNA) to inhibit HCV replication and to compare these molecules to canonical 21 nt siRNA. DsiRNA molecules were designed to target five distinct regions of the HCV genome -the 5'UTR and the coding regions for NS3, NS4B, NS5A or NS5B. These molecules were transfected into Huh7.5 cells that stably harboured an HCV subgenomic replicon expressing a firefly luciferase/neoR reporter (SGR-Feo-JFH-1) and were also tested on HCVcc-infected cells. All of the DsiRNAs inhibited HCV replication in both the subgenomic system and HCVcc-infected cells. When DsiRNAs were transfected prior to infection with HCVcc, the inhibition levels reached 99.5%. When directly compared, canonical siRNA and DsiRNA exhibited similar potency of virus inhibition. Furthermore, both types of molecules exhibited similar dynamics of inhibition and frequencies of resistant mutants after 21 days of treatment. Thus, DsiRNA molecules are as potent as 21 nt siRNAs for the inhibition of HCV replication and may provide future approaches for HCV therapy if the emergence of resistant mutants can be addressed.en
dc.description.affiliationSao Paulo State Univ, IBILCE, Genom Study Lab, Sao Jose Do Rio Preto, SP, Brazil
dc.description.affiliationUniv Leeds, Fac Biol Sci, Sch Mol &Cellular Biol, Leeds LS2 9JT, W Yorkshire, England
dc.description.affiliationUnespSao Paulo State Univ, IBILCE, Genom Study Lab, Sao Jose Do Rio Preto, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordination for the Improvement of Higher Level Personnel
dc.description.sponsorshipIdFAPESP: 2009/08534-9-BC
dc.description.sponsorshipIdCoordination for the Improvement of Higher Level Personnel: 5290/11-2-BC
dc.format.extent1-18
dc.identifierhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117742
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 10, n. 2, p. 1-18, 2015.
dc.identifier.doi10.1371/journal.pone.0117742
dc.identifier.fileWOS000350662100115.pdf
dc.identifier.issn1932-6203
dc.identifier.lattes7991082362671212
dc.identifier.orcid0000-0001-5693-6148
dc.identifier.urihttp://hdl.handle.net/11449/129564
dc.identifier.wosWOS:000350662100115
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.relation.ispartofjcr2.766
dc.relation.ispartofsjr1,164
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.titleEvaluation of canonical siRNA and dicer substrate RNA for inhibition of hepatitis C virus genome replication: a comparative studyen
dc.typeArtigo
dcterms.rightsHolderPublic Library Science
unesp.author.lattes7991082362671212[5]
unesp.author.orcid0000-0001-5693-6148[5]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt

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Artigos - Biologia - IBILCE