Overcoming thermostability challenges in mRNA-lipid nanoparticle systems with piperidine-based ionizable lipids

Maintaining the thermostability of mRNA/LNP systems remains challenging. This study investigates limiting the generation of aldehyde impurities that react with mRNA nucleosides through chemical engineering of lipids. Piperidine-based lipids improve the long-term storage stability of mRNA/LNPs at refrigeration temperature as a liquid formulation. Amine moieties of ionizable lipids play a vital role in limiting reactive aldehyde generation, mRNA-lipid adduct formation, and loss of mRNA function during storage. These findings highlight the importance of lipid design and help enhance the shelf-life of mRNA/LNP systems.

Kazuki Hashiba, Masamitsu Taguchi, Sachiko Sakamoto, Ayaka Otsu, Yoshiki Maeda, Hirofumi Ebe, Arimichi Okazaki, Hideyoshi Harashima, Yusuke Sato