Novel Ionizable Lipid Nanoparticles for SARS-CoV-2 Omicron mRNA Delivery.

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, series of ionizable LNPs are rationally designed. YK009-LNP is an optimal delivery platform to carry mRNA. YK009-LNP exhibited higher mRNA delivery efficiency, a more favorable biodistribution pattern, and better safety than the approved MC3-LNP. In addition, mRNA encoding SARS-CoV-2 Omicron receptor binding domain protein was synthesized, and intramuscular administration of mice with YK009-LNP-Omicron mRNA induced a robust immune response and immune protective effect. Our study provides a novel mRNA delivery vehicle with more powerful delivery efficiency and better safety than the approved LNPs. This article is protected by copyright. All rights reserved.