Current Advances in Nucleic Acid Based Antiviral Therapy

摘要

In recent years, the emergence and reemergence of infectious viral diseases has promoted intense research to explore new approaches for drug development. Targeting of a specific viral gene(s) to inhibit viral replication is one of the newly developing strategies of experimental research. In this regard, nucleic acid (NA)-based antiviral agents, such as ribozymes, antisense oligonucleotides, aptamers, short interfering RNA, MicroRNAs (miRNAs), and artificial miRNAs (AmiRNAs), represent a new collection of potential gene targeting tools. These therapeutic sequences can be designed to target the viral genome or messenger RNAs (mRNAs), leading to down regulation of a specific viral gene. Cellular miRNAs and DNA virus-encoded miRNAs play important roles in viral replication and pathogenesis. Thus, silencing of these miRNAs using specific inhibitors, such as antagomirs or miRNA sponges, is another promising strategy for inhibition of viral replication. AmiRNAs are mimics of endogenous miRNAs, which can be designed to target viral mRNAs and inhibit viral infection with mutational tolerance. The NA-based antiviral strategy has been applied experimentally to inhibit many RNA and DNA viruses, such as the highly pathogenic avian influenza (H5N1), SARSCoV, Hepatitis C virus (HCV), and Hepatitis B virus (HBV).This strategy has many advantages, particularly the drug specificity and high affinity to the viral gene targets. Here, we highlight current research progress in the field of viral gene targeting in regards to several viral diseases of both human and animal origin. Additionally, we discussed the limitations and pitfalls that pertain to this new class of antiviral therapies.