Lipid nanoparticles (LNPs) are important for biological research, vaccine development, cell transfection, etc. Unfortunately, in our experience, in vitro transfection does not directly translate to successful in vivo gene delivery. In this Advanced Healthcare Materials paper, which was an amazing collaboration with Merck Life Science, we designed and synthesized several novel unsaturated lipids with novel slightly more hydrophobic head groups and studied their LNPs. Most importantly, through intelligent design of the lipid structures (both headgroup and tail), we were able to develop LNPs without fusogenic activity in blood cells, with the right pKa, and finally with highly efficient mRNA delivery in vivo. I recommend reading this paper for those who work on lipid synthesis, LNPs, and vaccine development. Thanks to Eleni Samaridou, Johanna Simon, Moritz Beck-Broichsitter, Gary Davidson for the great joint project!
Check out the paper here.