biostudies-literatureLong JNational Natural Science Foundation of Chinae2202590https://www.ebi.ac.uk/biostudies/studies/S-EPMC11468017biostudies-literatureUnknown12(13)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.Advanced healthcare materialsNovel Ionizable Lipid Nanoparticles for SARS-CoV-2 Omicron mRNA Delivery.PMC1146801781830101Yang JYu CLu HZhang ZLong JWang SZhang HCao YWang XWang HSang YSong GfalseNovel 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, 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.2023-01-01T00:00:00Z2023 May2026-06-13T05:40:59.255Z2025-04-06T12:31:28.879ZS-EPMC114680173671670210.1002/adhm.202202590