Enhanced Pulmonary and Splenic mRNA Delivery Using DOTAP-Incorporated Poly(β-Amino Ester)-Lipid Nanoparticles

mRNA-based therapies hold tremendous promise for treating various diseases, yet their clinical success is hindered by delivery challenges. This study developed a library of 140 lipocationic Poly(β-amino ester)s (PBAEs) and formulated lipid-polymer hybrid nanoparticles (LPHs) with four helper lipids, including 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), to enhance mRNA delivery. Initial