Apolipoprotein E4 facilitates transfection of human monocyte-derived dendritic cells by lipid nanoparticles

The use of mRNA as a therapeutic drug class is a safe and fast alternative to viral vector or plasmid DNA therapies. Nevertheless, free mRNA will be rapidly degraded after administration to the body and only reach the cytosol of desired cells with difficulty. Lipid nanoparticles (LNP) safely deliver mRNA to cells of interest and can be used in the treatment of different diseases. Dendritic cells are the primary antigen-presenting cells and important for mRNA vaccine delivery. Efforts to increase LNP transfection of these cells are necessary and can be achieved by different approaches. Here, we present apolipoprotein E4 addition to LNP administration as one mean of increasing LNP-mediated eGFP mRNA delivery to human monocyte-derived dendritic cells. We also show some steps in the preparation method for LNP optimization using MS2 RNA as a novel model nucleic acid.