Polycations Improve Intracellular Stability of mRNA Delivered Using Lipid Nanoparticles for Prolonged Protein Expression

In the application of mRNA as vaccines and therapeutics, the short duration of protein expression poses significant challenges. This study demonstrates the potential of incorporating polycations into lipid nanoparticles (LNPs) to address this issue. For a straightforward evaluation of this approach, polycations were added to anionic LNPs, which shifted the surface charge from negative to positive with minimal impact on nanoparticle size. The polycation addition effectively protected the delivered mRNA from degradation in cultured cells, plausibly due to the prolonged association of polycations with mRNA inside cells. Consequently, this approach significantly extended the duration of protein expression from mRNA.