热稳定性
纳米颗粒
化学
哌啶
化学工程
生物化学
纳米技术
有机化学
材料科学
酶
工程类
作者
Kazuki Hashiba,Masamitsu Taguchi,Sachiko Sakamoto,Ayaka Otsu,Yoshiki Maeda,Hirofumi Ebe,Okazaki Arimichi,Hideyoshi Harashima,Yusuke Sato
标识
DOI:10.1038/s42003-024-06235-0
摘要
Abstract Lipid nanoparticles (LNPs) have emerged as promising platforms for efficient in vivo mRNA delivery owing to advancements in ionizable lipids. However, maintaining the thermostability of mRNA/LNP systems remains challenging. While the importance of only a small amount of lipid impurities on mRNA inactivation is clear, a fundamental solution has not yet been proposed. In this study, we investigate an approach to limit the generation of aldehyde impurities that react with mRNA nucleosides through the chemical engineering of lipids. We demonstrated that piperidine-based lipids improve the long-term storage stability of mRNA/LNPs at refrigeration temperature as a liquid formulation. High-performance liquid chromatography analysis and additional lipid synthesis revealed that amine moieties of ionizable lipids play a vital role in limiting reactive aldehyde generation, mRNA–lipid adduct formation, and loss of mRNA function during mRNA/LNP storage. These findings highlight the importance of lipid design and help enhance the shelf-life of mRNA/LNP systems.
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