Locked nucleic acid: modality, diversity, and drug discovery.

Autor: Hagedorn PH; Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Copenhagen, 2970 Hørsholm, Denmark., Persson R; Pharmaceutical Sciences, Roche Pharma Research and Early Development, Roche Innovation Center Copenhagen, 2970 Hørsholm, Denmark., Funder ED; Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Copenhagen, 2970 Hørsholm, Denmark., Albæk N; Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Copenhagen, 2970 Hørsholm, Denmark., Diemer SL; Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Copenhagen, 2970 Hørsholm, Denmark., Hansen DJ; Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Copenhagen, 2970 Hørsholm, Denmark., Møller MR; Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Copenhagen, 2970 Hørsholm, Denmark., Papargyri N; Department of Biotechnology and Biomedicine, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark., Christiansen H; Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Copenhagen, 2970 Hørsholm, Denmark., Hansen BR; Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Copenhagen, 2970 Hørsholm, Denmark., Hansen HF; Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Copenhagen, 2970 Hørsholm, Denmark., Jensen MA; Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Copenhagen, 2970 Hørsholm, Denmark., Koch T; Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Copenhagen, 2970 Hørsholm, Denmark. Electronic address: troels.koch@roche.com.
Jazyk: angličtina
Zdroj: Drug discovery today [Drug Discov Today] 2018 Jan; Vol. 23 (1), pp. 101-114. Date of Electronic Publication: 2017 Oct 06.
DOI: 10.1016/j.drudis.2017.09.018
Abstrakt: 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 improved pharmacological properties in vivo. Locked nucleic acid (LNA), which exhibits high binding affinity and potency, is widely used for this purpose. 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 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.
(Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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