Nature materialsSep 1, 2025

Peptides that deliver mRNA specifically to certain organs

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 28, 2026

Abstract

Essence

Surface peptide codes on lipid nanoparticles can steer systemic mRNA delivery toward selected extrahepatic organs.

Evidence

This delivery-platform study combined molecular dynamics with in vitro and in vivo testing to show that peptide-decorated LNPs can alter protein corona formation and thereby direct organ-selective delivery of mRNA, other RNAs, and gene-editing cargo after systemic administration.

Caveat

The abstract describes a modular preclinical targeting strategy, but it does not establish therapeutic benefit, long-term safety, or performance in humans.

Simplified

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 the hepatic delivery of mRNA using lipid nanoparticles (LNPs), current strategies for extrahepatic-organ-selective mRNA delivery still have limitations. Here we report a peptide-encoded organ-selective targeting (POST) method for the delivery of mRNA to extrahepatic organs after systemic administration, which is based on the modular tuning of LNPs through surface engineering with specific amino acid sequences (POST codes). Molecular dynamics simulations and in vitro and in vivo testing show that the organ-selective targeting of POST results from the specific protein corona of the peptide-decorated LNPs, which is established from the mechanical optimization of the binding affinities between peptides with a particular sequence and plasma proteins. This approach can be used for the organ-selective delivery of different ribonucleic acids and multiple gene editing machinery. Overall, the POST platform creates a modular repertoire for LNP surface engineering for directing organ tropism, broadening the scope and versatility of organ-selective delivery.