Aromatic mRNA-LNP platform confers vaccine protection with reduced off-target delivery

Lipid nanoparticles (LNPs) are clinically advanced vectors, as demonstrated by the COVID-19 vaccines. However, high hepatic tropism of these vaccines has been shown to induce liver disease.[1] Bioreducible and aromatic moieties mitigate this challenge due to their biodegradability and increased mRNA delivery compared to non-aromatic LNPs. This increase is likely due to aromatic rings’ ability to form pi-stacking bonds, which remain unexplored in vaccines.[2] Here, we build a library of bioreducible, aromatic ionizable lipids that elicit a strong immune response with reduced liver delivery.