Multiplexed lipid nanoparticle barcoding reveals tissue-dynamic kinetic insights and enriched cellular tropism in hepatic zones.

ABSTRACT: Lipid nanoparticles (LNPs) efficiently deliver nucleic acids to cells in vivo and facilitate clinical applications including RNA-based vaccines and therapies. Discovery and optimization of LNPs remain challenging due to the complexity of input variables and low throughput workflows. To accelerate these processes, we report a broadly compatible barcoded Cre recombinase mRNA barcode platform that enables multiplexed LNP tracking in vivo in tdTomato reporter mice. We evaluate accumulation and degradation kinetics of mRNA encapsulated in Selective Organ Targeting (SORT) LNPs in the liver, lung, and spleen, and show that functional protein activity is associated with rapid organ enrichment. We further demonstrate how barcode multiplexing can streamline systematic kinetic studies, distinguish na

SUBMITTER: Moore ST 

PROVIDER: S-EPMC12873177 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature