The vast majority of nucleic acid-loaded lipid nanoparticles contain cargo

No more than 16% of lipid nanoparticles (LNPs) are found to be empty in formulations for mRNA delivery.

• A significant portion of LNPs contain nucleic acid cargo and may exert functional effects.
• The correlation between LNP lipid formulation, preparation method, and nucleic acid cargo size with the proportion of empty LNPs is largely unexplored.
• The study utilized a single particle based method to analyze nucleic acid loading heterogeneity in LNPs.
• Only a minor fraction of LNPs were found to be empty, regardless of whether they were loaded with siRNA, mRNA, or plasmids.
• Standard LNP lipid-cargo combinations and preparation methods may yield LNPs that are capable of fulfilling their intended biomedical roles.

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