Introduction In the world of mRNA therapeutics and lipid nanoparticles (LNPs), PEG-lipids have long been treated as a default design choice . They are used to: Provide steric shielding to prevent aggregation Extend circulation time Reduce nonspecific interactions However, as mRNA technologies move beyond one-time vaccines toward repeat-dose systemic therapies , PEG-associated risks—most notably anti-PEG antibodies and the accelerated blood clearance (ABC) phenomenon —are bec