4180936 - Non-viral and efficient transfection agents for RNA delivery | Poster Board #M5

There is a growing demand for developing safe and efficient non-viral vectors for RNA transfection due to several drawbacks and risks associated with viral vectors. The most-established cationic polymers for gene transfection are linear polyethylenimines (PEI), albeit PEI has certain limitations such as high charge density that can damage the cells and poor transfection efficiency for RNA, especially compared to lipid nanoparticles (LNPs). Here, we will describe the synthesis of a library of PEI-co-polypropylenimine (PEI-co-PPI) copolymers and systematic investigation of their in-vitro and in vivo RNA transfection ability. PEI-co-PPI copolymers were found to be more efficient in vitro than the current state-of-the-art in vitro transfection agents while in vivo transfection was demonstrated to approach the performance of LNPs, but with much simpler and cheaper production of the RNA complexes. Further in-vitro transfection efficiency of PEI-co-PPI copolymer can be enhanced by PAOx-ylation which could be interesting for vaccination/protein replacement therapy and is currently under investigation.