Recent advances in analytical separation techniques for therapeutic oligonucleotides.

IF 1.8 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Bioanalysis Pub Date : 2025-09-26 DOI:10.1080/17576180.2025.2565141

Tímea Dérerová, Zuzana Vosáhlová, Květa Kalíková

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引用次数: 0

Abstract

Therapeutic oligonucleotides are an emerging class of drugs designed for gene expression modulation. The increasing number of clinical trials and currently expanding market is facilitating further integration and accessibility of these therapeutics. A crucial step in drug development involves reliable analytical tools for characterization and quality control. For clinical applications, oligonucleotides must be separated and purified to ensure regulatory compliance. However, their analysis represents a complex bioanalytical challenge, grounded in their complex impurity profiles. Chemical stability and binding affinity of oligonucleotide-based therapeutics are enhanced during synthesis by extensive modifications, inducing formation of various synthesis failures or truncated sequences. Furthermore, meeting current guidelines or addressing manufacturing scale-up strategies remains challenging as each oligonucleotide typically necessitates a custom analytical protocol. Here, we provide an overview of the most recent advances in separation methods, including various chromatography methods and capillary electrophoresis for nucleic acid-based therapeutics.

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治疗性寡核苷酸分析分离技术的最新进展。

治疗性寡核苷酸是一类用于基因表达调节的新兴药物。越来越多的临床试验和目前不断扩大的市场正在促进这些治疗方法的进一步整合和可及性。药物开发的一个关键步骤是使用可靠的分析工具进行表征和质量控制。对于临床应用，寡核苷酸必须分离和纯化，以确保符合法规。然而，他们的分析代表了一个复杂的生物分析挑战，基于他们复杂的杂质谱。基于寡核苷酸的治疗药物的化学稳定性和结合亲和力在合成过程中通过广泛的修饰，诱导各种合成失败或截断序列的形成而增强。此外，满足当前指南或解决生产规模战略仍然具有挑战性，因为每个寡核苷酸通常需要定制分析方案。在这里，我们概述了分离方法的最新进展，包括用于核酸治疗的各种色谱方法和毛细管电泳。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

3.30

自引率

16.70%

发文量

审稿时长

2 months

期刊介绍： Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing. The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality. Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing. The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques. Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.