CpG ODNs: Precision Immunotherapy and Recent Trends in Nano-Enabled Nucleotide Delivery

Synthetic ODNs (oligodeoxynucleotides) with immunostimulatory CpG (cytosine-phosphate-guanine) motifs induce an immune-mediated response, activating B cells, T cells, natural killer cells, and competent antigen-presenting cells (APCs). This activation stimulates T helper 1 (TH1) cell activity and induces the release of pro-inflammatory cytokines, making CpG ODNs effective as immunoprotectants, vaccination adjuvants, and antiallergens. The findings that toll-like receptors (TLRs) integrating both adaptive and innate immunity prompted greater interest in TLRs' immunostimulatory capabilities, activators, and effects. Potent adjuvants such as TLR agonists are crucial for effective vaccine formulations because they stimulate dendritic cells (DCs) to activate specific T-cells. Non-methylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) have proven to be successful adjuvants central to TLR9 receptor activation, facilitating the necessary innate immune signaling cascade. Artificially synthesized CpG ODNs are durable, cost-effective, and easy to produce, making them promising candidates for advanced studies on innate immunity and immunoprotection mechanisms. This review discusses CpG ODN-mediated immunomodulatory interventions, their potential as biomedical tools for specific diseases, recent advances in their applications, and related clinical trials from the past decade.