2. Academic Validation
  3. Advances in oligonucleotide drug delivery

Advances in oligonucleotide drug delivery

  • Nat Rev Drug Discov. 2020 Oct;19(10):673-694. doi: 10.1038/s41573-020-0075-7.
Thomas C Roberts 1 2,  Robert Langer 3,  Matthew J A Wood 4 5
Affiliations

Affiliations

  • 1 Department of Paediatrics, University of Oxford, Oxford, UK. [email protected].
  • 2 MDUK Oxford Neuromuscular Centre, University of Oxford, Oxford, UK. [email protected].
  • 3 Department of Chemical Engineering and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 4 Department of Paediatrics, University of Oxford, Oxford, UK. [email protected].
  • 5 MDUK Oxford Neuromuscular Centre, University of Oxford, Oxford, UK. [email protected].
PMID: 32782413 DOI: 10.1038/s41573-020-0075-7
Abstract

Oligonucleotides can be used to modulate gene expression via a range of processes including RNAi, target degradation by RNase H-mediated cleavage, splicing modulation, non-coding RNA inhibition, gene activation and programmed gene editing. As such, these molecules have potential therapeutic applications for myriad indications, with several oligonucleotide drugs recently gaining approval. However, despite recent technological advances, achieving efficient oligonucleotide delivery, particularly to extrahepatic tissues, remains a major translational limitation. Here, we provide an overview of oligonucleotide-based drug platforms, focusing on key approaches - including chemical modification, bioconjugation and the use of nanocarriers - which aim to address the delivery challenge.

Figures