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。

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research 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

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引用次数: 0

摘要

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。

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

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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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.