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, a series of ionizable...

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Published inAdvanced healthcare materials Vol. 12; no. 13; pp. e2202590 - n/a
Main Authors Long, Jinrong, Yu, Changxiao, Zhang, Honglei, Cao, Yiming, Sang, Ye, Lu, Haitao, Zhang, Zhen, Wang, Xin, Wang, Huanyu, Song, Gengshen, Yang, Jing, Wang, Shengqi
Format Journal Article
LanguageEnglish
Published Germany 01.05.2023
Subjects
Animals
COVID-19
Excipients
ionizable lipids
lipid nanoparticles
Liposomes
Mice
mRNA delivery
mRNA vaccines
Nanoparticles
RNA, Messenger - genetics
SARS-CoV-2 - genetics
SARS‐CoV‐2 Omicron variant
Tissue Distribution
mRNA vaccines
ionizable lipids
SARS-CoV-2 Omicron variant
lipid nanoparticles
mRNA delivery
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Summary: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. A novel ionizable lipid YK009 is developed for lipid nanoparticles (LNP) formulation. YK009, DSPC, cholesterol, and DMG‐PEG 2000 are mixed with mRNA by a microfluidic‐based procedure to form YK009‐LNP‐mRNA. The YK009‐LNP‐SARS‐CoV‐2 Omicron mRNA vaccine could trigger a robust humoral immune response and cellular immune response and immune protection against the SARS‐CoV‐2 Omicron variant in mice.
ISSN:2192-2640
2192-2659
DOI:10.1002/adhm.202202590