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KMID : 0364820070430030159
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Korean Journal of Microbiology
2007 Volume.43 No. 3 p.159 ~ p.165
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Development of Hepatitis C Virus (HCV) Genome-Targeting Hammerhead Ribozyme Which Activity Can Be Allosterically Regulated by HCV NS5B RNA Replicase
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Lee Chang-Ho
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Abstract
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For the development of basic genetic materials for specific and effective therapeutic approach to suppress multiplication
of hepatitis C virus (HCV), HCV internal ribosome entry site (IRES)-targeting hammerhead ribozyme which activity is allosterically regulated by HCV regulatory protein, NS5B RNA replicase, was developed. The ribozyme targeted most effectively to +382 nucleotide (nt) site of HCV IRES RNA. The allosteric ribozyme was designed to be composed of sequence of RNA aptamer to HCV NS5B, communication module sequence which can transfer structural transition for inducing ribozyme activity upon binding NS5B to the aptamer, and sequence of ribozyme targeting +382 nt of HCV IRES. Noticeably, we employed in vitro selection technology to identify the most appropriate communication module sequence which can induce ribozyme activity depending on the NS5B protein. We demonstrated that the ribozyme was nonfunctional either in the absence of any proteins or in the presence of control bovine serum albumin. In sharp contrast, the allosteric ribozyme can induce activity of cleavage reaction with HCV IRES RNA in the presence of the HCV NS5B protein. This allosteric ribozyme can be used as lead compound for specific and effective anti-HCV agent, tool for highthroughput
screening to isolate lead chemicals for HCV therapeutics, and ligand for biosensor system for HCV diagnosis.
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KEYWORD
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allosteric ribozyme, communication module, hammerhead ribozyme, HCV IRES, Hepatitis C virus, RNA aptamer
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