Novel cationic polymers for RNA vaccination (PEI-PPI-Vac)

SARS-CoV-2 mRNA vaccines are delivered with lipid nanoparticles (LNPs). However, LNPs have several disadvantages. First, the formulation of mRNA-LNP vaccines is complex as it involves 4 lipids, an organic solvent, a special microfluid mixing device and a final purification step. Moreover, the current LNPs are shielded with polyethylene glycol that can trigger in rare cases life-threatening hypersensitivity reactions. Cationic polymers are more simple and cost-effective alternatives for LNPs as they allow a single-step formulation and can easily be equipped with a non-PEG shield. Recent in vivo studies with our patented cationic polymers elucidated that some polymers induce a fast and short expression, while others induce a prolonged expression of mRNA. The former polymers are interesting for the delivery of RNA vaccines. These data now allow us to modulate the mRNA expression kinetics by using a rational polymer design. This project aims to further optimize the structure of our cationic polymers to increase their potential as RNA vaccine delivery system. With the most optimal polymer an in vivo vaccination proof-of-concept will be generated.