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通过优化辅助脂质,探索基于DOTAP的mRNA纳米粒子

Xueni Ma^1,2, Fanqi Wu^2,3, Caihong Peng⁴

¹Key Laboratory of Digestive Diseases, Lanzhou University Second Hospital, Lanzhou, China.

Biotechnology journal

|August 7, 2023

概括

这项研究表明,非脂物可以有效地替代基于DOTAP的脂质纳米粒子 (LNP) 中的辅助脂质,用于mRNA输送. 这些新型LNP配方在体外和体内都显示出有效的mRNA转染,具有器官特异性向和疫苗开发潜力.

科学领域:

生物技术和制药科学生物技术和制药科学
纳米医学和药物输送系统

背景情况:

脂质纳米颗粒 (LNP) 对于RNA传递至关重要,mRNA-LNP疫苗在COVID-19后获得了突出地位.
建立了基于DOTAP的LNP,但优化DOPE等辅助脂质是增强交付的关键.
以前的研究表明,非脂可以提高LNP的效率,促使对它们与DOTAP的使用进行调查.

研究的目的:

为了研究基于DOTAP的脂质纳米颗粒 (LNPs) 的配方,使用非脂辅助脂质进行mRNA输送.
在体外和体内评估这些新型LNP配方的mRNA转染效率.
评估优化LNP的治疗应用潜力,包括疫苗开发.

主要方法:

基于DOTAP的LNP配方与各种非脂辅助脂质配合,包括单甘油和胆固醇衍生物.
在实验室中评估由配方LNP调解的mRNA转染.
在体内评估mRNA表达和免疫反应,使用露西法酶mRNA模型和小鼠的SARS-CoV-2尖端mRNA.

主要成果:

具有不同脂肪酸链的单甘油 (C14:0,C16:0,C18:0,C18:1,C18:2) 有效调解了mRNA转染.
特定的非脂和胆固醇的结合提高了转染效率,LNP3-MO表现出卓越的性能.
在体内研究表明,肺和脏丰富LNP3-MO,并在免疫接种后成功诱导SARS-CoV-2尖端抗体.

结论:

非脂是DOTAP基LNP的可行和有前途的辅助脂质,提供了改进的mRNA传递能力.
基于DOTAP的优化LNP可以在体外和体内实现高效的mRNA转染,并针对特定器官进行向.
这些发现支持开发基于LNP的新型疗法和使用非脂成分的疫苗.

关键词:

在 DOTAP 中,我们可以使用 DOTAP.在SARS-CoV-2的尖端抗体.帮助性脂质是帮助性脂质.脂质纳米颗粒的使用方法提供mRNA的交付.非脂类的非脂类.

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