Abstract
Nucleic acid-based therapeutics have demonstrated their efficacy in the treatment of various diseases and vaccine development. Antisense oligonucleotide (ASO) technology exploits a single-strand short oligonucleotide to either cause target RNA degradation or sterically block the binding of cellular factors or machineries to the target RNA. Chemical modification or bioconjugation of ASOs can enhance both its pharmacokinetic and pharmacodynamic performance, and it enables customization for a specific clinical purpose. ASO-based therapies have been used for treatment of genetic disorders, cancer and viral infections. In particular, ASOs can be rapidly developed for newly emerging virus and their reemerging variants. This review discusses ASO modifications and delivery options as well as the design of antiviral ASOs. A better understanding of the viral life cycle and virus-host interactions as well as advances in oligonucleotide technology will benefit the development of ASO-based antiviral therapies.
Highlights
In 2019, the World Health Organization listed eight RNA viruses, including influenza, Zika, dengue, and severe acute respiratory syndrome-coronavirus (SARS-CoV), as the top threats to global health [1]
This review focuses on Antisense oligonucleotide (ASO) that are used for antiviral strategies
Oligonucleotide bioconjugates offer the potential for enhanced drug delivery, but recent advances in nanotechnology have further benefited the transport of therapeutic ASOs across biological barriers and improved their pharmacokinetics in circulating blood
Summary
In 2019, the World Health Organization listed eight RNA viruses, including influenza, Zika, dengue, and severe acute respiratory syndrome-coronavirus (SARS-CoV), as the top threats to global health [1]. Antiviral medicines, including small-molecule drugs and biologics, are still needed to combat emerging viral pathogens or prevent disease progression. Small-molecule drugs are the main class of therapeutics for treating various diseases and conditions. These drugs target and bind allosterically to disease-associated proteins and receptors or inhibit the activities of metabolic enzymes. Nucleic acid-based therapeutics can target a genetic culprit via complementary basepairing, and in this regard, this approach is superior to small-molecule or protein drugs—. The most widely used nucleic acids are ASOs and siRNAs that cause target RNA cleavage/degradation or block mRNA processing or translation. A single-stranded RNA or DNA that folds into a unique structure, binding its target molecule with a high affinity. TFO binding in general inhibits transcription or protein binding to DNA
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