Published online Dec 21, 2013. doi: 10.3748/wjg.v19.i47.8949
Revised: November 10, 2013
Accepted: November 28, 2013
Published online: December 21, 2013
Processing time: 107 Days and 11.9 Hours
In this review, we discuss recent advances in nucleic acid-based therapeutic technologies that target hepatitis C virus (HCV) infection. Because the HCV genome is present exclusively in RNA form during replication, various nucleic acid-based therapeutic approaches targeting the HCV genome, such as ribozymes, aptamers, siRNAs, and antisense oligonucleotides, have been suggested as potential tools against HCV. Nucleic acids are potentially immunogenic and typically require a delivery tool to be utilized as therapeutics. These limitations have hampered the clinical development of nucleic acid-based therapeutics. However, despite these limitations, nucleic acid-based therapeutics has clinical value due to their great specificity, easy and large-scale synthesis with chemical methods, and pharmaceutical flexibility. Moreover, nucleic acid therapeutics are expected to broaden the range of targetable molecules essential for the HCV replication cycle, and therefore they may prove to be more effective than existing therapeutics, such as interferon-α and ribavirin combination therapy. This review focuses on the current status and future prospects of ribozymes, aptamers, siRNAs, and antisense oligonucleotides as therapeutic reagents against HCV.
Core tip: Nucleic acids have emerged as new anti-hepatitis C virus (HCV) agents due to their great specificity, chemical synthesizability, pharmaceutical amenability, and broad targeting ability. Clinical applications of nucleic acids have been delayed due to their potential immunogenicity and toxicity, low efficacy, possible off-target effects, and lack of efficient delivery vehicles. However, recent advances in delivery carriers and chemical modification methods have improved the efficacy and bioavailability of nucleic acid-based agents. Hence, nucleic acids may be attractive anti-HCV options. In this report, the current status and future prospects of ribozymes, aptamers, siRNAs, and antisense oligonucleotides as anti-HCV regimens will be discussed.