Membrane-modified lipid nanoparticles for RNA delivery

Ribonucleic acid (RNA)-mediated gene regulation is being widely investigated in preclinical and clinical studies owing to its immense potential for treating a broad spectrum of medical conditions. Because unmodified RNA molecules are rapidly degraded and cleared from circulation, carriers such as lipid nanoparticles (LNPs) are used to protect them, deliver them to target tissues, and facilitate their cellular entry and endosomal escape. However, most LNPs are trafficked to the liver upon intravenous administration, so new approaches are being explored to facilitate extrahepatic delivery. Recent studies suggest that modifying RNA-loaded LNPs with cell-derived phospholipid membranes can alter their biodistribution, cellular entry, and gene regulation potency, resulting in improved therapeutic outcomes. This review discusses the status of membrane-modified LNPs for RNA delivery, highlights key design criteria for these systems, and provides perspectives on the path toward clinical implementation. With further development, these exciting tools could enable RNA-based therapies to realize their full clinical potential.