Inhibition of Hepatitis C Virus (HCV) Replication by Hammerhead Ribozyme Which Activity Can Be Allosterically Regulated by HCV NS5B RNA Replicase

C형 간염바이러스(HCV)의 NS5B RNA Replicase에 의해 활성이 유도되는 Hammerhead 리보자임에 의한 HCV 복제 억제 연구

  • Lee, Chang-Ho (Department of Molecular Biology and Institute of Nanosensor and Biotechnology, Dankook University) ;
  • Lee, Seong-Wook (Department of Molecular Biology and Institute of Nanosensor and Biotechnology, Dankook University)
  • 이창호 (단국대학교 자연과학부 나노센서 바이오텍 연구소 분자생물학과) ;
  • 이성욱 (단국대학교 자연과학부 나노센서 바이오텍 연구소 분자생물학과)
  • Received : 2011.09.05
  • Accepted : 2011.09.20
  • Published : 2011.09.30

Abstract

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.

Keywords

allosteric hammerhead ribozyme;HCV IRES;hepatitis C virus;RNA aptamer

Acknowledgement

Supported by : 한국학술진흥재단

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