Biodistribution of lipid nanoparticle, eGFP mRNA and translated protein following subcutaneous administration in mouse.

IF 1.8 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS Bioanalysis Pub Date : 2024-01-01 Epub Date: 2024-06-28 DOI:10.1080/17576180.2024.2360361

Åsa Sandelius, Humaira Naseer, Johnny Lindqvist, Amanda Wilson, Neil Henderson

引用次数: 0

Abstract

Aim: Increased knowledge of biodistribution and pharmacokinetics of lipid nanoparticle (LNP)-encapsulated mRNA drug components may aid efficacy and safety evaluation.Methods: Mice were subcutaneously administrated LNP encapsulated enhanced green fluorescent protein mRNA and sampled up to 72 h after dosing. LNP, mRNA and translated protein were quantified by LC-MS, branched DNA and ELISA.Results: Highest levels of LNP and mRNA were detected in skin, followed by spleen, but also rapidly distributed to circulation. Translated protein showed high concentration in skin and spleen, but also in liver and kidney across 24 h where the LNP was cleared at 4 h.Conclusion: Subcutaneously dosing LNP encapsulated mRNA in mice resulted in a nonlinear relationship of LNP, mRNA and protein concentration across multiple tissues.

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小鼠皮下注射脂质纳米粒子、eGFP mRNA 和翻译蛋白后的生物分布。

目的：增加对脂质纳米粒子（LNP）包裹的 mRNA 药物成分的生物分布和药代动力学的了解，有助于疗效和安全性评估。方法：给小鼠皮下注射 LNP：给小鼠皮下注射 LNP 封装的增强型绿色荧光蛋白 mRNA，并在给药后 72 小时内采样。通过 LC-MS、支链 DNA 和 ELISA 对 LNP、mRNA 和翻译蛋白进行定量。结果：皮肤中检测到的 LNP 和 mRNA 含量最高，其次是脾脏，但也迅速分布到血液循环中。翻译蛋白在皮肤和脾脏中浓度较高，但在肝脏和肾脏中的浓度也超过了 24 小时，其中 LNP 在 4 小时后被清除：给小鼠皮下注射 LNP 封装的 mRNA 会导致 LNP、mRNA 和蛋白质在多个组织中的浓度呈非线性关系。

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.