Suppression of Hepatitis C Viral Genome Replication with RNA-Cleaving Deoxyribozyme

Abstract

Downregulation of viral genes via oligonucleotide-based gene therapy is a potential strategy for the treatment of virus infection such as hepatitis C. Hepatitis C virus (HCV) is a small-sized, enveloped, positive-sense single-stranded RNA virus. As HCV has highly mutative properties and strong drug resistance, effective antiviral drug for HCV infection is currently unavailable. One of the potential therapeutic strategies for hepatitis C treatment is to cleave HCV RNA genome with proper antisense nucleic acids, thereby inhibiting virus replication in host. RNA-cleaving antisense oligodeoxyribozyme, known as DNAzyme, is an attractive therapeutic oligonucleotide which enables cleavage of mRNA in a sequence-specific manner and thus silencing target gene. In this chapter, we discuss current status of functional antisense oligonucleotides that have been applied to inhibit HCV replication in vitro and in vivo. In particular, the DNAzyme and the DNAzyme conjugated nanoparticle system are discussed in detail to demonstrate a successful usage of functional oligonucleotide and its delivery in vivo for further therapeutic application of functional oligonucleotides in the treatment of hepatitis C.