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KMID : 0364820110470030188
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Korean Journal of Microbiology
2011 Volume.47 No. 3 p.188 ~ p.193
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Inhibition of Hepatitis C Virus (HCV) Replication by Hammerhead Ribozyme Which Activity Can Be Allosterically Regulated by HCV NS5B RNA Replicase
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Lee Chang-Ho
Lee Seong-Wook
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Abstract
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As a specific and effective therapeutic genetic material against hepatitis C virus (HCV) multiplication, HCV internal ribosome entry site (IRES)-targeting hammerhead ribozyme which activity is allosterically regulated by HCV regulatory protein, NS5B RNA replicase, was constructed. The allosteric ribozyme was 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 nucleotide of HCV IRES. With real-time PCR analysis, the ribozyme was found to efficiently inhibit HCV replicon replication in cells. Of note, the allosteric ribozyme was shown to inhibit HCV replicon replication more efficiently than either HCV genome-targeting ribozyme or NS5B aptamer only. This allosteric ribozyme can be used as a lead genetic agent for the specific and effective suppression of HCV replication.
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KEYWORD
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allosteric hammerhead ribozyme, HCV IRES, hepatitis C virus, RNA aptamer
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