NRT-FX is an RNA-based therapeutic that restores macrophage-mediated immune homeostasis by modulating miRNA signals derived from necroptotic hepatocytes. In the MASH microenvironment, hepatocytes undergoing necroptosis continuously transmit “don’t eat me” signals through the CD47-SIRPα axis, while reduced TSP1 expression suppresses macrophage phagocytic activity.
NRT-FX inhibits let-7i-5p, leading to increased TSP1 expression and restoration of “eat me” signaling, thereby promoting the clearance of necroptotic hepatocytes. This process reduces the release of pro-inflammatory cytokines and suppresses the activation of hepatic stellate cells (HSCs), ultimately alleviating liver inflammation and fibrosis.