Peptide codes for organ-selective mRNA delivery

Organ-selective delivery of messenger RNA (mRNA) is critical for fulfilling the therapeutic potential of mRNA-based gene and protein replacement technologies. Despite clinical advances in hepatic delivery of mRNA using lipid nanoparticles (LNPs), strategies for extrahepatic organ-selective mRNA delivery remain underexplored. Here, we report a strategy, termed peptide-encoded organ-selective targeting (POST), that allows digital programming of LNPs, through surface engineering with specific amino acid sequences (POST codes), to deliver mRNA to extrahepatic organs after systemic administration.