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Advances in oligonucleotide drug delivery
Thomas C Roberts1,2, Robert Langer3, Matthew J A Wood4,5
1Department of Paediatrics, University of Oxford, Oxford, UK. thomas.roberts@paediatrics.ox.ac.uk.
Nature Reviews. Drug Discovery
|August 13, 2020
Summary
Oligonucleotide therapeutics offer versatile gene modulation for various diseases. Overcoming delivery challenges, especially to non-liver tissues, is key for their broader clinical success.
Area of Science:
- Molecular Biology
- Drug Delivery
- Therapeutics
Background:
- Oligonucleotides modulate gene expression through diverse mechanisms like RNA interference and target degradation.
- Approved oligonucleotide drugs highlight their therapeutic potential for numerous indications.
- Efficient delivery, particularly to extrahepatic sites, remains a significant hurdle for oligonucleotide-based therapies.
Purpose of the Study:
- To provide an overview of oligonucleotide-based drug platforms.
- To highlight strategies for overcoming oligonucleotide delivery challenges.
- To focus on chemical modification, bioconjugation, and nanocarrier approaches.
Main Methods:
- Review of chemical modification strategies for oligonucleotides.
- Analysis of bioconjugation techniques to enhance oligonucleotide properties.
- Examination of nanocarrier systems for oligonucleotide delivery.
- Focus on approaches targeting extrahepatic tissues.
Main Results:
- Oligonucleotide platforms utilize chemical modifications, bioconjugation, and nanocarriers to improve delivery.
- These strategies aim to enhance stability, targeting, and cellular uptake of oligonucleotides.
- Progress in these areas is crucial for expanding therapeutic applications beyond the liver.
Conclusions:
- Chemical modification, bioconjugation, and nanocarriers are key strategies to enhance oligonucleotide delivery.
- Addressing delivery limitations is essential for realizing the full therapeutic potential of oligonucleotides.
- Further advancements are needed to enable efficient oligonucleotide-based treatments for a wider range of diseases.
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