| Download | - View accepted manuscript: The efficacy of siRNAs against Hepatitis C virus Is strongly influenced by structure and target site accessibility (PDF, 1.3 MiB)
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| DOI | Resolve DOI: https://doi.org/10.1016/j.chembiol.2010.04.011 |
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| Author | Search for: Sagan, Selena M.1; Search for: Nasheri, Neda1; Search for: Luebbert, Christian1; Search for: Pezacki, John Paul1 |
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| Affiliation | - National Research Council of Canada. NRC Steacie Institute for Molecular Sciences
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| Format | Text, Article |
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| Abstract | Hepatitis 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. |
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| Publication date | 2010-05-28 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NPARC number | 17104550 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | e270685b-9556-4301-9cc3-10d8be69b0b4 |
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| Record created | 2011-03-15 |
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| Record modified | 2020-04-17 |
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