Nature Communications (Jul 2022)
An LNA-amide modification that enhances the cell uptake and activity of phosphorothioate exon-skipping oligonucleotides
- Ysobel R. Baker,
- Cameron Thorpe,
- Jinfeng Chen,
- Laura M. Poller,
- Lina Cox,
- Pawan Kumar,
- Wooi F. Lim,
- Lillian Lie,
- Graham McClorey,
- Sven Epple,
- Daniel Singleton,
- Michael A. McDonough,
- Jack S. Hardwick,
- Kirsten E. Christensen,
- Matthew J. A. Wood,
- James P. Hall,
- Afaf H. El-Sagheer,
- Tom Brown
Affiliations
- Ysobel R. Baker
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- Cameron Thorpe
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- Jinfeng Chen
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- Laura M. Poller
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- Lina Cox
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- Pawan Kumar
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- Wooi F. Lim
- Department of Paediatrics, University of Oxford
- Lillian Lie
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- Graham McClorey
- Department of Paediatrics, University of Oxford
- Sven Epple
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- Daniel Singleton
- ATDBio Ltd, School of Chemistry, University of Southampton
- Michael A. McDonough
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- Jack S. Hardwick
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- Kirsten E. Christensen
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- Matthew J. A. Wood
- Department of Paediatrics, University of Oxford
- James P. Hall
- Department of Pharmacy, Chemistry and Pharmacy Building, University of Reading
- Afaf H. El-Sagheer
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- Tom Brown
- Department of Chemistry, University of Oxford, Chemistry Research Laboratory
- DOI
- https://doi.org/10.1038/s41467-022-31636-2
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 11
Abstract
Oligonucleotides targeting mRNA are promising therapeutic agents but suffer from poor bioavailability. Here, the authors develop reduced-charge oligonucleotides with artificial LNA-amide linkages with improved cell uptake and minimal structural deviation to the DNA:RNA duplex.
