Related Experiment Video
Updated: Sep 2, 2026
Testing the In Vitro and In Vivo Efficiency of mRNA-Lipid Nanoparticles Formulated by Microfluidic Mixing
Published on: January 20, 2023
Nitric oxide-assisted lipid nanoparticles amplify mRNA vaccine responses
Zhengwei Liu1, Dinglingge Cao1, Xucheng Hou1
1Department of Immunology and Immunotherapy, Windreich Department of Artificial Intelligence and Human Health, Department of Oncological Sciences, Icahn Genomics Institute, Charles Bronfman Institute for Personalized Medicine, Precision Immunology Institute, Tisch Cancer Center, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States.
Abstract:
mRNA vaccines have made substantial clinical advances, yet their full clinical potential can be further expanded by enhancing cytosolic delivery. Here, we integrate a nitric oxide (NO) generator with lipid nanoparticles (LNPs) to boost mRNA delivery efficiency and mRNA-based vaccine efficacy. SM-102/DEA LNPs, the lead formulation, achieved significantly higher mRNA delivery compared with the FDA approved SM-102 LNPs in both cellular and animal models. The intramuscular administration of SM-102/DEA LNPs encapsulating mRNA encoding SARS-CoV-2 spike protein elicited substantially higher anti-spike IgG levels and robust CD8+ and CD4+ T cell responses compared to SM-102 LNPs. Mechanistic studies revealed that DEA incorporation promotes endosomal escape of mRNA cargos in SM-102/DEA LNPs. These findings establish NO-assisted LNPs as a unique platform for potent mRNA delivery, which provides a new paradigm for overcoming endosomal barriers and improving the efficacy of mRNA vaccines.
