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The spleen, as the largest peripheral immune organ, is rich in T cells, B cells, NK cells, and dendritic cells (DCs), and plays a central role in immune response regulation and tumor immune surveillance. Spleen targeted transfection reagents achieve selective enrichment in the spleen through optimized lipid composition without the need for targeting ligand modifications, enabling efficient transfection of ASO, siRNA, mRNA, circRNA, and other nucleic acids in both animal models and cells.