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对酸脂丰富的LNP进行的对比研究,用于mRNA疫苗的输送

Burcu Binici¹, Zahra Rattray², Yvonne Perrie²

¹Strathclyde Institute of Pharmacy and Biomedical Sciences, 161 Cathedral St, University of Strathclyde, Glasgow G4 0RE, UK; Faculty of Pharmacy, Department of Pharmaceutical Technology, Ege University, Bornova, 35100 Izmir, Türkiye.

International journal of pharmaceutics

|July 7, 2025

概括

将DOTAP等阴离子脂质纳入脂质纳米颗粒 (LNP) 可以改善局部mRNA的表达,并减少肝脏的非向输送. 然而,这些修改对小鼠的免疫性产生了有限的长期益处.

科学领域:

生物技术是生物技术.
疫苗学疫苗学疫苗学
纳米医学是一种纳米医学.

背景情况:

脂质纳米颗粒 (LNP) 对于mRNA疫苗的输送至关重要.
肌肉内注射可能会导致肝脏中意外的LNP表达.
酸脂被探索以提高LNP的性能和局部化.

研究的目的:

调查是否将阴性脂质 (DOTAP,DODAP) 纳入基于ALC-0315的LNP可以改善局部mRNA的表达和免疫性.
评估不同阴性脂质度对LNP特征和生物活性的影响.
评估修改后的LNP降低非目标肝部表达的潜力.

主要方法:

通过部分用DOTAP (5-50%) 或DODAP (10-50%) 取代ALC-0315来制定LNP.
描述LNP的物理化学特性,包括泽塔潜力和形态.
在体外转染效率测试.
在小鼠注射后的体内mRNA表达分析.
在小鼠中使用卵蛋白 (OVA) mRNA-LNP 的免疫性研究.

主要成果:

用DODAP (10-25%) 进行部分替代,对LNP的特性和表达影响极小.
完全用DODAP替代降低了体内LNP强度.
纳入DOTAP (5-25%) 增加了正泽塔潜力,改变了形态,增强了体外转染,并增强了局部表达.
10%的DOTAP降低了肝脏表达,表明局部化得到改善.
5%的DOTAP增强了后期的IgG反应,但在增强剂后差异减少,没有显示长期免疫性优势.

结论:

将DOTAP纳入ALC-0315 LNP可以增强局部mRNA表达并减少肝脏LNP积累.
在高度下,DODAP显示出有限的益处,并可能降低LNP功效.
虽然DOTAP改善了最初的免疫反应,但没有观察到长期益处,这表明疫苗开发的局限性.

关键词:

在 DOTAP 中,我们可以使用 DOTAP.免疫性免疫性免疫性肌肉内注射肌肉内注射脂质组成脂质组成脂质纳米颗粒的使用方法提供mRNA疫苗的方法.

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