Antisense DNA and RNA agents against picornaviruses.
Anti-picornaviral antisense agents are part of a broader group of nucleic acid-based molecules developed for sequence-specific inhibition of translation and/or transcription of the target sequence through induced nuclease activity or physical hindrance. Three types of nucleic acid-based gene silencing molecules can be distinguished, including DNA-base antisense oligonucleotides (ASO), nucleic acid enzymes (ribozyme and DNAzyme) and double-stranded small interfering RNA (siRNA or microRNA). These antisense DNA and RNA molecules have been widely studied for gene functional studies and therapeutic purposes. In this review, we focus on drug development using ASO and siRNA strategies to inhibit picornavirus infections. The picornavirus genome organization and life cycle is described, followed by discussion of design considerations, chemical modifications and drug delivery approaches. Recent studies using antisense against picornavirus are reviewed. Finally, we compare the advantages and disadvantages of the antisense agents with those of other therapeutics, taking into consideration their limitations which need to be overcome to achieve the final goal of clinical application.
Providence Heart and Lung Institute, Department of Pathology and Laboratory Medicine, University of British Columbia-St. Paul's Hospital, Vancouver, Canada.
Travis
T
Lim
Jane
J
Yuan
Huifang Mary
HM
Zhang
Alhousseynou
A
Sall
Zhen
Z
Liu
Yue
Y
Su
Decheng
D
Yang
D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016373:DNA, Antisense / Q000008:administration & dosage / Q000627:therapeutic use*; D016679:Genome, Viral; D006801:Humans; D008081:Liposomes; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D010849:Picornaviridae / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D010850:Picornaviridae Infections / Q000188:drug therapy*; D020543:Proteome; D016372:RNA, Antisense / Q000008:administration & dosage / Q000627:therapeutic use*; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use
D000998:Antiviral Agents; D016373:DNA, Antisense; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D020543:Proteome; D016372:RNA, Antisense; D034741:RNA, Small Interfering