Exceptional Uptake, Limited Protein Expression: Liver Macrophages Lost in Translation of Synthetic mRNA

To investigate the translation and function of nucleic acid, we designed and prepared LNPs co-encapsulating GFP mRNA and TLR4 siRNA. These LNPs were administered via tail vein injection and primarily accumulated in the liver. Therefore, in this experiment, we isolated liver cells and used flow cytometry to sort Kupffer cells for gene sequencing, aiming to study the mRNA expression levels in different cell types. Overall design: After treating mice with different LNPs for 16 hours, Kuffer cells and hepatocytes were isolated for RNA sequencing.