Novel Ionizable Lipid Nanoparticles for SARS‐CoV‐2 Omicron mRNA Delivery

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.