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Improving siRNA design targeting nucleoprotein gene as antiviral against the Indonesian H5N1 virus
Authors:Risza Hartawan  Dwi Ari Pujianto  Ni Luh Putu Indi Dharmayanti  Amin Soebandrio
Institution:1.Doctoral Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.;2.Indonesian Research Center for Veterinary Science, Ministry of Agriculture, Bogor 16114, Indonesia.;3.Department of Medical Biology Pre Clinic, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.;4.Eijkman Institute, Ministry of Research, Technology and Higher Education, Jakarta 10430, Indonesia.
Abstract:BackgroundSmall interfering RNA technology has been considered a prospective alternative antiviral treatment using gene silencing against influenza viruses with high mutations rates. On the other hand, there are no reports on its effectiveness against the highly pathogenic avian influenza H5N1 virus isolated from Indonesia.ObjectivesThe main objective of this study was to improve the siRNA design based on the nucleoprotein gene (siRNA-NP) for the Indonesian H5N1 virus.MethodsThe effectiveness of these siRNA-NPs (NP672, NP1433, and NP1469) was analyzed in vitro in Marbin-Darby canine kidney cells.ResultsThe siRNA-NP672 caused the largest decrease in viral production and gene expression at 24, 48, and 72 h post-infection compared to the other siRNA-NPs. Moreover, three serial passages of the H5N1 virus in the presence of siRNA-NP672 did not induce any mutations within the nucleoprotein gene.ConclusionsThese findings suggest that siRNA-NP672 can provide better protection against the Indonesian strain of the H5N1 virus.
Keywords:influenza in birds  H5N1 subtype  Indonesia  RNA interference  antiviral agents
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