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体育领域中的寡核苷酸疗法?反兴奋剂视角。

Oligonucleotide therapeutics in sports? An antidoping perspective.

作者信息

Parr Maria K, Keiler Annekathrin M

机构信息

Institute of Pharmacy, Pharmaceutical and Medicinal Chemistry, Freie Universität Berlin, Berlin, Germany.

Institute of Doping Analysis & Sports Biochemistry, Kreischa, Germany.

出版信息

Arch Pharm (Weinheim). 2025 Jan;358(1):e2400404. doi: 10.1002/ardp.202400404. Epub 2024 Oct 24.

Abstract

Within the last two decades, the European Medicines Agency and the US Food and Drug Administration have approved several gene therapies. One category is oligonucleotide therapeutics, which allow for the regulation of the expression of target genes. Besides already approved therapeutics, there are several preclinical and clinical trials ongoing. The World Anti-Doping Agency prohibits the use of "nucleic acids or nucleic acid analogs that may alter genome sequences and/or alter gene expression by any mechanism" as a nonspecified method at all times. Hence, the administration of nucleic acids or analogs by athletes would cause an Anti-Doping Rule Violation. Herein, we discuss types of oligonucleotide therapeutics, their potential to be misused in sports, and considerations to sample preparation and mass spectrometric approaches with regard to antidoping analysis.

摘要

在过去二十年中,欧洲药品管理局和美国食品药品监督管理局已批准了几种基因疗法。其中一类是寡核苷酸疗法,它可以调节靶基因的表达。除了已获批的疗法外,还有多项临床前和临床试验正在进行。世界反兴奋剂机构始终禁止将“可能通过任何机制改变基因组序列和/或改变基因表达的核酸或核酸类似物”作为一种未明确规定的方法使用。因此,运动员使用核酸或类似物将导致违反反兴奋剂规则。在此,我们讨论寡核苷酸疗法的类型、它们在体育领域被滥用的可能性,以及在反兴奋剂分析中样品制备和质谱方法的注意事项。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26be/11704058/d5c36e351222/ARDP-358-e2400404-g004.jpg

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