Abstract
The potential of antisense oligonucleotides in gene silencing was discovered over 40 years ago, which resulted in the growing interest in their chemistry, mechanism of action, and metabolic pathways. This review summarizes the selected mechanisms of antisense drug action, as well as therapeutics which are to date approved by the Food and Drug Administration and European Medicines Agency. Moreover, bioanalytical methods used for ASO pharmacokinetics and metabolism studies are briefly summarized. Special attention is paid to the primary pharmacokinetic properties of the different chemistry classes of antisense oligonucleotides. Moreover, in vivo and in vitro metabolic pathways of these compounds are widely described with the emphasis on the different animal models as well as in vitro models, including tissues homogenates, enzyme solutions, and human liver microsomes.
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