Crosslinking Strategy Enhances Stability and Delivery of mRNA Lipid Nanoparticles
Researchers developed a post-assembly crosslinking approach that improves the structural stability and endosomal escape efficiency of mRNA lipid nanoparticles, potentially expanding applications for RNA therapeutics and vaccines.
Lipid nanoparticles (LNPs) have enabled the effective delivery of RNA therapeutics and mRNA vaccines. However, their broader applications are limited by suboptimal stability and endosomal escape efficiency. Researchers have now presented a readily adoptable post-assembly crosslinking approach that enhances the structural and functional stability of mRNA LNPs.
By leveraging a series of cholesterol derivatives and crosslinking methods, the research team induced crosslinks between the lipid components following mRNA LNP assembly, forming crosslinked LNPs (cLNPs). The researchers systematically evaluated crosslinking parameters and identified the optimal conditions that enhance both the physical stability and transfection efficiency of cLNPs.
The findings demonstrate that cLNPs exhibit improved structural integrity under storage and lyophilization conditions, and increased extracellular stability and endosomal escape efficiency, resulting in improved performance of mRNA LNPs both in vitro and in vivo. This crosslinking strategy enables more resilient formulations and expands the applicability of LNP-based therapies for gene therapy and vaccine delivery.
The work lays the foundation for next-generation LNPs with enhanced stability and delivery efficiency, amplifying the impact of RNA therapeutics and vaccines. The data supporting the findings of this study are available in the Article and its Supplementary Information.