Oligonucleotide therapeutics: chemistry, delivery and clinical progress.
Oligonucleotide therapeutics have the potential to become a third pillar of drug development after small molecules and protein therapeutics. However, the three approved oligonucleotide drugs over the past 17 years have not proven to be highly successful in a commercial sense. These trailblazer drugs have nonetheless laid the foundations for entire classes of drug candidates to follow. This review will examine further advances in chemistry that are earlier in the pipeline of oligonucleotide drug candidates. Finally, we consider the possible effect of delivery systems that may provide extra footholds to improve the potency and specificity of oligonucleotide drugs. Our overview focuses on strategies to imbue antisense oligonucleotides with more drug-like properties and their applicability to other nucleic acid therapeutics.
Department of Chemistry & Institute for Life Sciences, University of Southampton, Highfield, Southampton, SO17 1BJ, UK.|RNA Therapeutics Institute & Department of Biochemistry & Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Vivek K
VK
Sharma
Department of Chemistry & Institute for Life Sciences, University of Southampton, Highfield, Southampton, SO17 1BJ, UK.|RNA Therapeutics Institute & Department of Biochemistry & Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Jonathan K
JK
Watts
D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D016174:Hepacivirus / Q000187:drug effects; D006801:Humans; D009841:Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*
D000998:Antiviral Agents; D009841:Oligonucleotides