Tailored Monoacyl Poly(2-oxazoline)- and Poly(2-oxazine)-Lipids as PEG-Lipid Alternatives for Stabilization and Delivery of mRNA-Lipid Nanoparticles.

The successful use of lipid nanoparticles (LNPs) for clinical development of the COVID-19 mRNA vaccines marked a breakthrough in mRNA-LNP therapeutics. As one of the vital components of LNPs, poly(ethylene glycol)-lipid conjugates (PEG-lipids) influence particle biophysical properties and stability, as well as interactions within biological environments. Reports suggesting that anti-PEG antibodies can be detected quite commonly within the human population raise concerns that PEG content in commercial LNP products could further stimulate immune responses to PEG.