Design principles of lipid nanoparticles for RNA delivery
摘要
Lipid nanoparticles can serve as safe and effective delivery vehicles for RNA therapies by facilitating RNA encapsulation, cell uptake and endosomal escape, enabling precise control of protein expression. Beyond their established role in prophylactic vaccines, formulations of lipid nanoparticles with RNA are being explored in cancer immunotherapy, protein replacement and gene therapy. In this Review, we examine the design landscape of RNA–lipid-nanoparticle formulations, detailing their key components, formation, physicochemical properties and methods of characterization. We discuss how the composition and stoichiometry of the constituents of lipid nanoparticles influence delivery efficiency, tissue targeting and clearance in vivo. Finally, we highlight major therapeutic applications and outline future directions from both engineering and translational perspectives.