Most lipid nanoparticles (LNPs) given intravenously end up in the liver, so reaching other tissues often requires high doses. This Nature Protocols paper from the University of Pennsylvania gives a step-by-step guide for building targeted LNPs (tLNPs) by attaching whole antibodies or antibody fragments to the particle surface using standard laboratory equipment. In mouse examples, an anti-PECAM-1 antibody raised lung transfection about five-fold, and an anti-EGFR antibody raised liver transfection about 20-fold compared with untargeted particles. In primary human T cells tested ex vivo, anti-CD5 conjugation increased uptake 4.5-fold and improved mRNA transfection. The authors say the approach is modular and works with any LNP formulation or antibody. The goal is a reproducible workflow that supports lower doses and clinical translation of precision nucleic acid therapies.
