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.

Keywords

OligonucleotideComputational biologyBioconjugationRNase HRNARNA splicingRNA interferenceRNase PGeneBiologyChemistryGeneticsBiochemistry

MeSH Terms

Drug ApprovalDrug Delivery SystemsGene Expression RegulationHumansOligonucleotides

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Publication Info

Year
2020
Type
review
Volume
19
Issue
10
Pages
673-694
Citations
1799
Access
Closed

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Thomas C. Roberts, Róbert Langer, Matthew J. A. Wood (2020). Advances in oligonucleotide drug delivery. Nature Reviews Drug Discovery , 19 (10) , 673-694. https://doi.org/10.1038/s41573-020-0075-7

Identifiers

DOI
10.1038/s41573-020-0075-7
PMID
32782413
PMCID
PMC7419031

Data Quality

Data completeness: 86%