A precision-engineered dendritic cell-targeted mRNA nanovaccine for enhanced antiviral immunity

<h2>Summary</h2> Messenger RNA (mRNA) vaccines have shown great therapeutic potential across multiple disease conditions, yet their success primarily depends on effective delivery strategies. Synthetic lipid-like nanoparticles (LLNs), leveraging biomimetic properties and adaptable surface chemistry, emerged as advanced vehicles for targeted mRNA vaccines with high efficacy and low toxicity. Here, we developed a dendritic cell (DC)-targeted LLN platform that incorporated a CD47-derived self-peptide (SP) to reduce macrophage phagocytosis and a mannose ligand to enhance DC uptake. Our results showed that the synergistic dual modification of these LLNs with SP and mannose (SM-LLNs) substantially increased mRNA expression in lymph nodes (LNs). Additionally, SM-LLNs promoted DC maturation, enhanced antigen-specific T cell production, and elicited potent and sustained antiviral immune responses. These findings underscore the critical role of ligand modification in mRNA vaccine design and highlight our dual-modified LLN platform as a promising approach for enhancing mRNA-based vaccinations.