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核心技术专利：CN118964589B侵权必究
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杂交 LC-MS/MS 法分析抗体-寡核苷酸偶联物中游离反义寡核苷酸有效荷载。

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

机构信息

Drug Metabolism & Pharmacokinetics, Biogen, 225 Binney St, Cambridge, MA 02142, USA.

Current address: Denali Therapeutics, 161 Oyster Point Blvd., South San Francisco, CA 94080, USA.

出版信息

Bioanalysis. 2024;16(15):791-800. doi: 10.1080/17576180.2024.2368339. Epub 2024 Jul 23.

DOI:10.1080/17576180.2024.2368339
PMID:39041663
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11415018/
Abstract

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. 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). 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.

摘要

反义寡核苷酸 (ASO) 已与各种部分缀合，例如肽、抗体或抗体的 Fab 区域，以增强其递送至靶组织的能力。定量游离的 ASO（ASO 有效载荷）对于描述其药代动力学/药效学 (PK/PD) 特性和肽/抗体/Fab ASO 缀合物递送后的生物分布至关重要。我们开发了一种基于杂交的 LC-MS/MS 方法，用于在 Fab-ASO 和带有接头的 ASO（ASO-linker）存在的情况下定量组织中的游离 ASO。该方法已应用于测量经 Fab-ASO 给药的小鼠肝和比目鱼肌中游离 ASO 的浓度。该方法还应用于其他抗体-ASO 和 Fab-ASO 缀合物在各种组织和血浆/血清样本中的游离 ASO 生物分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0321/11415018/472ee6f246a3/IBIO_A_2368339_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0321/11415018/10b4b8d8447a/IBIO_A_2368339_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0321/11415018/a926b734084d/IBIO_A_2368339_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0321/11415018/db438957a176/IBIO_A_2368339_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0321/11415018/472ee6f246a3/IBIO_A_2368339_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0321/11415018/10b4b8d8447a/IBIO_A_2368339_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0321/11415018/a926b734084d/IBIO_A_2368339_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0321/11415018/db438957a176/IBIO_A_2368339_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0321/11415018/472ee6f246a3/IBIO_A_2368339_F0004_C.jpg

相似文献

[1]
Bioanalysis of free antisense oligonucleotide payload from antibody-oligonucleotide conjugate by hybridization LC-MS/MS.

Bioanalysis. 2024

[2]
Validation and application of hybridization liquid chromatography-tandem mass spectrometry methods for quantitative bioanalysis of antisense oligonucleotides.

Bioanalysis. 2022-5

[3]
Hybridization Liquid Chromatography-Tandem Mass Spectrometry: An Alternative Bioanalytical Method for Antisense Oligonucleotide Quantitation in Plasma and Tissue Samples.

Anal Chem. 2020-8-4

[4]
Microflow LC-MS/MS to improve sensitivity for antisense oligonucleotides bioanalysis: critical role of sample cleanness.

Bioanalysis. 2022-11

[5]
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Drug Metab Dispos. 2022-3

[6]
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[7]
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Bioanalysis. 2018-10-1

[8]
Development of a Versatile High-through-put Oligonucleotide LC-MS Method to Accelerate Drug Discovery.

AAPS PharmSciTech. 2024-10-10

[9]
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Bioanalysis. 2022-5

[10]
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J Control Release. 2016-3-28

引用本文的文献

[1]
Quantitative Determination of Click-Reactive Antisense Oligonucleotide and Its Reactivity in Rat Brains by Hybridization LC-MS/MS to Support Pretargeted PET Imaging.

Anal Chem. 2025-6-17

[2]
Regulated bioanalysis of antibody-drug conjugates using LC-MS.

Bioanalysis. 2025-4

本文引用的文献

[1]
Targeting the transferrin receptor to transport antisense oligonucleotides across the mammalian blood-brain barrier.

Sci Transl Med. 2024-8-14

[2]
A validated capillary microsampling liquid chromatography-tandem mass spectrometry method for quantification of antisense oligonucleotides in mouse serum.

Bioanalysis. 2023-6

[3]
Targeted tissue delivery of RNA therapeutics using antibody-oligonucleotide conjugates (AOCs).

Nucleic Acids Res. 2023-7-7

[4]
A Novel Hybridization LC-MS/MS Methodology for Quantification of siRNA in Plasma, CSF and Tissue Samples.

Molecules. 2023-2-8

[5]
Microflow LC-MS/MS to improve sensitivity for antisense oligonucleotides bioanalysis: critical role of sample cleanness.

Bioanalysis. 2022-11

[6]
RNA-targeted therapeutics in cardiovascular disease: the time is now.

Eur Heart J Cardiovasc Pharmacother. 2022-12-15

[7]
Targeted Delivery of Antisense Oligonucleotides Through Angiotensin Type 1 Receptor.

Nucleic Acid Ther. 2022-8

[8]
Validation and application of hybridization liquid chromatography-tandem mass spectrometry methods for quantitative bioanalysis of antisense oligonucleotides.

Bioanalysis. 2022-5

[9]
Oligonucleotide Therapeutics: From Discovery and Development to Patentability.

Pharmaceutics. 2022-1-22

[10]
Quantification of Antisense Oligonucleotides by Splint Ligation and Quantitative Polymerase Chain Reaction.

Nucleic Acid Ther. 2022-2

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