Therapeutic mRNA-LNPs require design principles distinct from vaccines. Optimizing ionizable lipids, modifying or replacing PEG-lipids, and applying rational molecular design can improve immune compatibility, safety, and repeated-dose efficacy. These strategies reduce toxicity, unintended immune activation, and accelerated blood clearance, unlocking the full therapeutic potential of mRNA-LNPs beyond the vaccine paradigm.
Wei et al. (Mon,) studied this question.