Bioanalysis of free antisense oligonucleotide payload from antibody-oligonucleotide conjugate by hybridization LC-MS/MS.

IF 1.8 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS Bioanalysis Pub Date : 2024-01-01 Epub Date: 2024-07-23 DOI:10.1080/17576180.2024.2368339

Di Jiang, Pei Li, Long Yuan

引用次数: 0

Abstract

Background: Antisense oligonucleotides (ASOs) have been conjugated to various moieties, such as peptides, antibodies or Fab regions of antibodies, to enhance their delivery to target tissues. The quantitation of free ASO (ASO payload) is critical to characterize its pharmacokinetics/pharmacodynamics (PK/PD) properties and biodistribution after delivery of the peptide/antibody/Fab ASO conjugates.Results: We developed a hybridization-based LC-MS/MS methodology for quantification of free ASO in tissues in the presence of Fab-ASO and ASO with linker (ASO-linker).Conclusion: The developed method was applied to measure accurately the free ASO concentrations in liver and gastrocnemius in mice that were dosed with Fab-ASO. This methodology has also been applied to free ASO bioanalysis for other antibody-ASO and Fab-ASO conjugates in various tissues and plasma/serum samples.

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通过杂交 LC-MS/MS 对抗体-寡核苷酸共轭物中游离的反义寡核苷酸有效载荷进行生物分析。

背景：反义寡核苷酸（ASO）已与各种分子（如肽、抗体或抗体的 Fab 区）共轭，以增强其向靶组织的递送。游离 ASO（ASO 有效载荷）的定量对于表征其药代动力学/药效学（PK/PD）特性以及肽/抗体/Fab ASO 共轭物递送后的生物分布至关重要。结果：我们开发了一种基于杂交的 LC-MS/MS 方法，用于在 Fab-ASO 和 ASO 与连接体（ASO-连接体）存在的情况下定量组织中的游离 ASO。结论：所开发的方法可用于精确测量服用 Fab-ASO 的小鼠肝脏和腓肠肌中的游离 ASO 浓度。该方法还可用于各种组织和血浆/血清样品中其他抗体-ASO和Fab-ASO共轭物的游离ASO生物分析。

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.