Effective mRNA Delivery by Condensation with Cationic Nanogels Incorporated into Liposomes

Abstract

The challenge in effective delivery of mRNA has beena major hurdlein their development as therapeutics. Herein, we present that theincorporation of cationic nanogels as the condensing material formRNA into liposomes enables stable and enhanced mRNA delivery to cells in vitro. We prepared dextran-based nanogel particles, whichwere surface functionalized with oligoarginine peptide (DNPR9) andcomplexed with mRNA for incorporation into liposomes (LipoDNPR9).The use of DNPR9 with the liposomes resulted in enhanced internalization,as well as a 4-fold increase in transfection of luciferase mRNA whentreated with A549 cells in vitro, compared to controlliposomes. The enhancement in transfection efficiency was also observedin various cell lines while causing low cytotoxicity. The versatilityof the strategy was also investigated by applying DNPR9 for mRNA condensationto ionizable lipid particles, which resulted in an similar to 55% increasein transfection. The current development based on nanogel-incorporatedliposomes introduces an effective platform for mRNA delivery, whilethe condensation strategy using DNPR9 can be widely applied for variouslipid-based formulations to enhance their efficacy.