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In vivo and in vitro studies of antisense oligonucleotides – a review

机译：体内和体外研究反义寡核苷酸 - 综述

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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.
机译：在40年前发现基因沉默中的反义寡核苷酸的潜力，导致对其化学，作用机制和代谢途径的兴趣日益增长。本综述总结了反义药物行动的选定机制，以及食品和药物管理局和欧洲药物局批准的迄今为止的治疗方法。此外，简要概述了用于ASO药代动力学和代谢研究的生物分析方法。特别注意反义寡核苷酸的不同化学类别的主要药代动力学特性。此外，在这些化合物的体内和体外代谢途径中被广泛描述，重点是不同的动物模型以及体外模型，包括组织匀浆，酶溶液和人肝微粒体。

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