Distribution and biotransformation of therapeutic antisense oligonucleotides and conjugates
| Autor: | Lars Weidolf, Xue-Qing Li, Anders Dahlén, Shalini Andersson, Marie Elebring, David Janzén, Peter Gennemark, Mikko Hölttä, Anders Björkbom |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Drug Bioanalysis Time Factors media_common.quotation_subject Pharmacology 03 medical and health sciences 0302 clinical medicine Drug Development Biotransformation Drug Discovery Animals Humans Distribution (pharmacology) Tissue Distribution media_common Chemistry Oligonucleotide Disposition Oligonucleotides Antisense 030104 developmental biology 030220 oncology & carcinogenesis Antisense oligonucleotides Conjugate |
| Zdroj: | Drug Discovery Today. 26:2244-2258 |
| ISSN: | 1359-6446 |
| Popis: | Drug properties of antisense oligonucleotides (ASOs) differ significantly from those of traditional small-molecule therapeutics. In this review, we focus on ASO disposition, mainly as characterized by distribution and biotransformation, of nonconjugated and conjugated ASOs. We introduce ASO chemistry to allow the following in-depth discussion on bioanalytical methods and determination of distribution and elimination kinetics at low concentrations over extended periods of time. The resulting quantitative data on the parent oligonucleotide, and the identification and quantification of formed metabolites define the disposition. Proper quantitative understanding of disposition is pivotal for nonclinical to clinical predictions, supports communication with health agencies, and increases the probability of delivering optimal ASO therapy to patients. |
| Databáze: | OpenAIRE |
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