biostudies-literatureUnknown121(11)Francia VLipid nanoparticle (LNP) formulations are a proven method for the delivery of nucleic acids for gene therapy as exemplified by the worldwide rollout of LNP-based RNAi therapeutics and mRNA vaccines. However, targeting specific tissues or cells is still a major challenge. After LNP administration, LNPs interact with biological fluids (i.e., blood), components of which adsorb onto the LNP surface forming a layer of biomolecules termed the "biomolecular corona (BMC)" which affects LNP stability, biodistribution, and tissue tropism. The mechanisms by which the BMC influences tissue- and cell-specific targeting remains largely unknown, due to the technical challenges in isolating LNPs and their corona from complex biological media. In this study, we present a new technique that utilizes magnetiProceedings of the National Academy of Sciences of the United States of Americae2307803120https://www.ebi.ac.uk/biostudies/studies/S-EPMC10945860biostudies-literatureA magnetic separation method for isolating and characterizing the biomolecular corona of lipid nanoparticles.PMC10945860Zhang YWitzigmann DFrancia VSchiffelers RMCullis PRCheng MHYfalseA magnetic separation method for isolating and characterizing the biomolecular corona of lipid nanoparticles.Lipid nanoparticle (LNP) formulations are a proven method for the delivery of nucleic acids for gene therapy as exemplified by the worldwide rollout of LNP-based RNAi therapeutics and mRNA vaccines. However, targeting specific tissues or cells is still a major challenge. After LNP administration, LNPs interact with biological fluids (i.e., blood), components of which adsorb onto the LNP surface forming a layer of biomolecules termed the "biomolecular corona (BMC)" which affects LNP stability, biodistribution, and tissue tropism. The mechanisms by which the BMC influences tissue- and cell-specific targeting remains largely unknown, due to the technical challenges in isolating LNPs and their corona from complex biological media. In this study, we present a new technique that utilizes magneti2024-01-01T00:00:00Z2024 Mar2026-07-14T22:48:29.394Z2025-02-19T03:09:09.561ZS-EPMC109458603843754210.1073/pnas.2307803120