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对mRNA脂质纳米颗粒的研究在非冷条件下保质期稳定性

Anne-Gaëlle Reinhart¹, Anja Osterwald², Philippe Ringler³

¹Roche Pharma Research and Early Development, Therapeutic Modalities, pCMC, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Basel 4070, Switzerland.

Molecular pharmaceutics

|November 17, 2023

概括

mRNA脂质纳米粒子 (LNPs) 可以在不冷的情况下长时间保持活性. 这项研究发现,像C12-200这样的特定LNP在室温下保持功能,从而缓解了mRNA技术的存储和运输挑战.

科学领域:

纳米技术纳米技术
生物技术是生物技术.
制药科学制药科学

背景情况:

mRNA脂质纳米颗粒 (LNP) 对于药物和疫苗的输送至关重要.
目前的mRNA LNP配方需要冷存储,这带来了后勤和成本方面的挑战.
开发稳定,非冷的储存条件对于更广泛的mRNA LNP应用至关重要.

研究的目的:

在非冷储存条件下评估mRNA LNP的稳定性和活性.
为了确定在环境温度下保持功能的mRNA LNP配方.
了解影响LNP稳定的结构-活动关系.

主要方法:

使用微流体技术合成了五种结构多样化的mRNA LNP,其中包括多种可离子脂质 (C12-200,CCK-E12,MC3,SM-102,脂质23).
在2-8°C,25°C和40°C使用分析技术 (水力动力直径,泽塔潜力,封装效率,多分散性) 评估了9周的保质期稳定性.
在HEK293细胞中通过EGFP蛋白表达评估了体外活性,并使用冷EM分析了LNP架构.

主要成果:

大多数LNP在非冷储存期间,其物理特征 (大小,电荷,封装) 的变化很小.
里博格林测定表明mRNA含量一致,但体外活性有显著差异.
LNP 1 (C12-200) 和LNP 4 (SM-102) 的初始转化效率很高.
在2-8°C和25°C下,LNP 1 (C12-200) 保持了11周的活性.
在2-8°C时,LNP 4 (SM-102) 保持活力,但在25°C时在11周内下降.

结论:

特定的mRNA LNP配方,特别是那些含有C12-200脂质的配方,显示出非冷存储和运输的潜力.
试验室活性测定对于评估LNP功能至关重要,因为物理稳定性指标可能具有误导性.
了解LNP架构和结构-活动关系是克服存储限制和扩大mRNA LNP应用超越疫苗的关键.

关键词:

欧洲粮食计划署 (EGFP) 是一个全球粮食计划署.这就是LC-MS.在LNP中使用LNP.分析分析分析电子显微镜的电子显微镜它们是mRNARNA.货架寿命货架寿命稳定的稳定性稳定的稳定性

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