Locked nucleic acid: modality, diversity, and drug discovery

Peter H. Hagedorn, Robert Persson, Erik D. Funder, Nanna Albæk, Sanna L. Diemer, Dennis J. Hansen, Marianne R Møller, Natalia Papargyri, Helle Christiansen, Bo R. Hansen, Henrik F. Hansen, Mads A Jensen, Troels Koch*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Over the past 20 years, the field of RNA-targeted therapeutics has advanced based on discoveries of modified oligonucleotide chemistries, and an ever-increasing understanding of how to apply cellular assays to identify oligonucleotides with pharmacological properties in vivo. Locked nucleic acid (LNA), which exhibits high binding affinity and potency, is widely used. Our understanding of RNA biology has also expanded tremendously, resulting in new approaches to engage RNA as a therapeutic target. Recent observations indicate that each oligonucleotide compound is a unique entity, and small structural differences between oligonucleotides can often lead to substantial differences in their pharmacological properties. Here, we outline new principles for drug discovery exploiting oligonucleotide diversity to identify rare molecules with unique pharmacological properties.
Original languageEnglish
JournalDrug Discovery Today
Volume23
Issue number1
Pages (from-to)101-114
ISSN1359-6446
DOIs
Publication statusPublished - 2018

Bibliographical note

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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