Novel Ionizable Lipid Nanoparticles for SARS‐CoV‐2 Omicron mRNA Delivery
Jinrong Long, Changxiao Yu, Honglei Zhang, Yiming Cao, Ye Sang, Haitao Lü, Zhen Zhang, Xin Wang, Huanyu Wang, Gengshen Song, Jing Yang, Shengqi Wang
Abstract
mRNA-based therapy has emerged as the most promising nucleic acid therapy in the fight against COVID-19. However, a safe and efficacious systemic delivery remains a challenge for mRNA therapy. Lipid nanoparticles (LNPs) are currently widely used in mRNA delivery vehicles. Here, a series of ionizable LNPs is rationally designed. YK009-LNP is an optimal delivery platform to carry mRNA. YK009-LNP exhibits higher mRNA delivery efficiency, a more favorable biodistribution pattern, and better safety than the approved MC3-LNP. In addition, mRNA encoding severe acute respiratory syndrome coronavirus 2 Omicron receptor binding domain protein is synthesized and intramuscular administration of mice with YK009-LNP-Omicron mRNA induces a robust immune response and immune protective effect. A novel mRNA delivery vehicle with more powerful delivery efficiency and better safety than the approved LNPs is provided here.