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An LNA-amide modification that enhances the cell uptake and activity of phosphorothioate exon-skipping oligonucleotides

Authors :
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
Source :
Nature Communications, Vol 13, Iss 1, Pp 1-11 (2022)
Publication Year :
2022
Publisher :
Nature Portfolio, 2022.

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.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
13
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.9f5986b8806645e7a8826174637171fa
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-022-31636-2