Lipid nanoparticle (LNP)/mRNA complexes have great therapeutic potential but their PEG chains can induce the production of anti-PEG antibodies. New LNPs that do not contain PEG are greatly needed. We demonstrate here that poly-glutamic acid-ethylene oxide graft copolymers can replace the PEG on LNPs and outperform PEG-LNPs after chronic administration.