The efficacy of siRNAs against Hepatitis C virus Is strongly influenced by structure and target site accessibility

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DOIResolve DOI: http://doi.org/10.1016/j.chembiol.2010.04.011
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TypeArticle
Journal titleChemistry and Biology
Volume17
Issue5
Pages515527; # of pages: 13
AbstractHepatitis C virus (HCV) is a global health problem. Designing therapeutic agents that target HCV’s RNA genome remains challenging. HCV genomic RNA is large and highly structured with long-range genome-scale ordered RNA structures. Predicting the secondary- and tertiary-structure elements that reveal the accessibility of target sites within HCV RNA is difficult because of the abundance of longrange interactions. Target site accessibility remains a significant barrier to the design of effective therapeutics such as small interfering RNAs (siRNAs) against different strains of HCV. Here we developed two methods that interrogate the folding of HCV RNA, an approach involving viral RNA microarrays (VRMs) and an HCV viral RNA-coated magnetic bead-based (VRB) assay. VRMs and VRBs were used to determine target site accessibility for siRNAs designed against the HCV genome. Both methods predicted potency of siRNAs in cell-culture models for HCV replication that are not easily predicted by informatics means.
Publication date
LanguageEnglish
AffiliationNRC Steacie Institute for Molecular Sciences; National Research Council Canada
Peer reviewedYes
NPARC number17104550
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Record identifiere270685b-9556-4301-9cc3-10d8be69b0b4
Record created2011-03-15
Record modified2016-05-09
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