Peptide-modified lipid for organ-specific mRNA delivery

Lipid nanoparticle-based messenger RNA (mRNA) delivery system have ushered in a new era of gene therapeutics. However, their clinical advances have been impeded by the inherent liver tropism of lipid nanoparticles (LNPs), which limits extrahepatic applications. Herein, we highlight two recent studies written in Nature Materials. Guided by surface interface molecular mechanics, Chang and his colleagues worked on the intelligent design of targeted peptides combined with lipids. Concurrently, Lin and his colleagues explored novel organ-specific peptide-lipid materials and analyzed important LNP traits that co-determined the in vitro/in vivo transfection discrepancy. The resulting peptide-modified lipids exhibit the capacity for targeted delivery to various organs and realize gene editing function. These studies jointly established a modular platform that provides a rational and predictable strategy for designing tissue-specific LNPs, thereby paving the way for next-generation mRNA-based therapeutics.