The effect of miR192-LNP on the regulation of innate immune response

Previously, we demonstrated that microRNA-192 (miR-192) is an aging-associated immune-regulatory microRNA suppressing the hyperinflammatory state observed in the elderly (Tsukamoto T et al., iScience, 2020). In this study, we utilized lipid nanoparticle (LNP) technology to deliver miR-192 into the macrophage cells and investigated its mechanism of inflammation regulation and potential therapeutic applications. Murine macrophage RAW264.7 cells were pretreated with miR-192-LNP for 24 hours, followed by stimulation with lipopolysaccharide (LPS). To assess the impact of miR-192-LNP on the innate immune response against LPS, we performed bulk RNA sequencing (RNA-seq) to analyze gene expression alterations. Overall design: To examine the effect of miR-192-containing lipid nanoparticles (LNPs) on the innate immune response, RAW264.7 cells were pretreated with miR-192-LNP or negative control miRNA (NC)-LNP (containing 100 pmol miRNA) for 24 hours, followed by stimulation with 200 ng/mL LPS for an additional 24 hours. Gene expression profiles were obtained by RNA sequencing (RNA-seq) from six experimental groups: nonLNP_-, NC-LNP_-, miR192-LNP_-, nonLNP_LPS, NC-LNP_LPS, miR192-LNP_LPS), each with three biological replicates.