Advanced materials (Deerfield Beach, Fla.)Jan 28, 2026

Using Tagged mRNA to Quickly Find Lipid Nanoparticles That Target Tissues Outside the Liver for Immune Engineering

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Barcoded mRNA screening identified lipid nanoparticles with extrahepatic delivery and a lead formulation that improved mouse melanoma immunoengineering versus a standard mRNA LNP.

Evidence

Formulation/platform experiment screened 122 LNPs in vivo, tested a lead candidate in a syngeneic mouse melanoma model, and used single-particle protein-corona characterization to study organ transfection patterns.

Caveat

The therapeutic result is preclinical and shown in one mouse tumor model against one comparator, not in human disease.

Simplified

Interest continues to grow in the use of mRNA vaccines and therapeutics. While effective for immunization against infectious diseases, lipid nanoparticle (LNP) formulations used for other mRNA delivery applications suffer from off-target accumulation, poor immune transfection, and reactogenicity, limiting their application to immunoengineering. Development of new mRNA LNPs is severely bottlenecked by the LNP discovery process, which is historically low-throughput due to reliance on low-plex measurements. Here, we develop a high-throughput in vivo mRNA LNP screening platform based on barcoded mRNA (b-mRNA). Using this b-mRNA screening platform to simultaneously evaluate 122 LNPs, we identify novel LNP formulations capable of potent hepatic and extrahepatic transfection. We evaluate a lead LNP candidate for in situ immune modulation in a syngeneic mouse model of melanoma and demonstrate a significant reduction in tumor burden and extended survival compared to mice treated with a gold standard mRNA LNP formulation. We employ novel biochemical characterization techniques to analyze nanoparticle protein corona formation with single-particle resolution and gain insight into the influence of protein adsorption on hepatic and splenic transfection. Together, our results demonstrate the value of advanced LNP screening and characterization techniques for the development of next-generation mRNA LNPs for immunoengineering.