Nucleic acid-based gene-silencing molecules as potential antiviral therapeutics

Ji Yuan, Zhongbin Chen, Paul Cheung, David Chau, Decheng Yang

Research output: Contribution to journalReview article

2 Scopus citations

Abstract

The sequencing of many human viral genomes and the elucidation of molecular mechanisms of viral replication as well as signal transduction pathways involved in viral pathogenesis have provided unprecedented opportunities for the development of new therapeutics. One type of the most promising molecules in drug development is the nucleic-acid-based therapeutics, including antisense oligodeoxyribonucleotides (AODN), ribozymes, DNAzyme and small interfering RNA (siRNA). AODNs have shown great potential as powerful tools in gene functional studies, as well as highly selective therapeutic agents in drug development. Although several problems have been encountered such as toxicity, non-stability, side effects, and low intracellular uptake, there has been at least one antisense drug approved for the treatment of cytomegalovirus retinitis, and over twenty other antisense candidates are undergoing clinical trials. Ribozymes and DNAzymes, by binding to substrate RNA through base pairing, offer sequence-specific cleavage of disease-associated RNA transcripts and show great potential for development of novel antiviral agents. RNA interference has emerged as a novel tool that offers great hope and promise to study gene functions and to develop therapeutics against viral infection. This powerful antiviral effect is mediated by siRNAs that target the viral mRNA for degradation by cellular enzymes. The potential of siRNA to treat or prevent diseases in clinical settings remains to be proven. This article first overviews current nucleic acid-based approaches in gene silencing, and then focuses on the potential applications in antiviral therapy including our own data on coxsackieviral infection.

Original languageEnglish (US)
Pages (from-to)323-333
Number of pages11
JournalDrug Design Reviews Online
Volume2
Issue number4
DOIs
StatePublished - Jun 2005

Keywords

  • Antisense ODN
  • Antiviral agents
  • Coxsackievirus B3
  • DNAzyme
  • Ribozymes
  • Small interfering RNA

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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