Specific inhibition of hepatitis C virus expression by antisense oligodeoxynucleotides : in vitro model for selection of target sequence

作者: T. Wakita , J.R. Wands

DOI: 10.1016/S0021-9258(17)36775-3

关键词: Sense (molecular biology)Hepatitis C virusVirologyVirusOpen reading frameMolecular biologyUntranslated regionGene expressionViral replicationNucleic acid sequenceBiology

摘要: Abstract The effect of sense and antisense oligodeoxynucleotides (ODNs) on hepatitis C virus (HCV) gene expression was studied to determine the role highly conserved 5'-untranslated region in life cycle virus. It found that ODNs complementary nucleotides (nt) 38-65, 134-175, 312-339 5' noncoding 341-377 core open reading frame efficiently blocked HCV RNA translation. Overlapping differed by only several showed substantially different inhibition Fine sequence specificity testing at nt positions 351-377 revealed as small a 12-mer (nt 351-363) retained high degree (80%) inhibitory activity compared longer sequences. These results suggest there are three specific domains immediately downstream initiation codon may be critical for translation RNA. This study also provides an experimental approach selection target sequences susceptible effects, well definition functional regions genome necessary viral replication.

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