Targeted delivery of lipid nanoparticle-mRNA formulations modified with ligand pattern to dendritic cells based on DNA origami

mRNA vaccines have gained considerable attentions in prevention and treatment of virus infections, cancer and genetic diseases, especially in the application to the COVID-19 pandemic in recent years.

Due to the immunogenicity and instability of mRNA, the in vivo delivery of mRNA plays a crucial role in vaccine efficacy.

Among various materials, lipid nanoparticles (LNPs) have shown to be one of the most potent carriers for mRNA delivery and successfully enter the clinic.

To further improve vaccine efficacy, dendritic cells (DC) uptake can be optimized by decorating mannose ligands on LNP-mRNA formulations for targeted vaccine delivery.

However, the effect of ligand density, spatial distance and organization pattern on cellular uptake remains poorly understood.

Due to the addressability of DNA origami, nanoparticles and small molecules can be spatially organized into prescribed pattern with nanoscale precision.

Therefore, we propose to develop designed ligand patten on LNP-mRNA formulations by transferring ligand pattern distributed on DNA origami to LNPs.

With ligands modified on surface, LNP-mRNA formulations will be used to investigate the effect of ligand pattern on DC uptake, which is not accessible to other targeted delivery system. The results of the project will promote the development of vaccine delivery field.

In addition, it will influence the health care and biomaterial industries, which are central to Europe’s ongoing and future economic success.