Synthesis and Characterization of Polymer-based mRNA Delivery Carrier

Abstract

Messenger RNA (mRNA) delivery has the potential for high therapeutic efficacy to treat a variety of diseases. Since the COVID-19 pandemic, more research is being done on lipid nanoparticles (LNP), which are FDA-approved for use in coronavirus vaccines, but they have several drawbacks, including excessive immune response and off-target effects. To overcome these disadvantages of LNPs, we sought to develop a polymer-based mRNA delivery system. Utilizing poly(β-amino ester) (PBAE) in this study, a library of 55 PBAEs was established, distinguished by pH responsiveness and biodegradability. In vivo screening experiments, 20 PBAEs were selected that exhibited higher long-term expression than LNPs. Finally, we focused on four types of polymers (4C, 8B, 8C, 8D) for characterization, and in the case of 8C, we also identified differences in mRNA expression based on polymer molecular weight. Subsequent research based on the analysis of selected polymers and in vivo experiments may lead to mRNA therapeutics that can be applied to various diseases.