Molecular Design Principles to Target mRNA Delivery With One-Component Ionizable Amphiphilic Janus Dendrimers Derived From Plant Phenolic Acids

Viral and synthetic vectors for the delivery of nucleic acids were key to the rapid development of the extraordinarily efficient Covid-19 vaccines and of genetic nanomedicine. The four-component lipid nanoparticles, statistically distributed in nanoparticles, are the leading delivery non-viral vector used by BioNTech/Pfizer and Moderna to access their Covid-19 mRNA vaccines. Here we report the molecular design principles to target mRNA delivery and activity with a one-component ionizable multifunctional amphiphilic Janus dendrimer system derived from plant phenolic acids. The precise location of the functional groups in the one-component system demonstrates target being induced by the hydrophilic region and activity by the hydrophobic domain of the Janus. These principles, and a hypothetic mechanism explaining them, simplify preparation, handling and storage of vaccines, reduce price, while employing renewable starting materials. Therefore, an increased accessibility to a large diversity of mRNA-based vaccines and nanotherapeutics may become available by simple molecular design principles.