CpGODN

CpGODN, short for CpG oligodeoxynucleotides, are short synthetic DNA sequences that include unmethylated cytosine-guanine (CpG) motifs. These motifs resemble bacterial and viral DNA and can activate the innate immune system through Toll-like receptor 9 (TLR9), primarily in endosomal compartments of plasmacytoid dendritic cells and B cells.

Mechanism and immunology

CpGODN stimulate a MyD88-dependent signaling pathway that leads to the production of pro-inflammatory cytokines such as IL-6, IL-12, TNF-α, and type I interferons. They promote maturation of dendritic cells, enhance antigen presentation, and bias adaptive immunity toward a Th1-type response, supporting cellular and humoral immunity. Different CpGODN designs produce distinct immunostimulatory profiles, which is central to their use as adjuvants or immunotherapies.

Chemistry and design

Typical CpGODN are about 18–24 nucleotides long. To resist nuclease degradation, many CpGODN employ a phosphorothioate backbone, though phosphodiester backbones or mixed chemistries are also used for specific applications. Based on their immunostimulatory profiles, CpGODN are commonly categorized into CpG-A, CpG-B, and CpG-C variants, each with characteristic effects on cytokine production and B cell activation.

Applications and clinical use

CpGODN have been investigated as vaccine adjuvants to enhance antibody and T cell responses, and as components of cancer immunotherapies and infectious disease vaccines. Several CpGODN formulations have progressed through clinical trials, highlighting their potential to boost immunity while requiring careful attention to dosing and safety.

History

The CpG motif’s immunostimulatory activity was identified in the 1990s, with key work by researchers including Timothy A. Krieg contributing to the development of CpGODN reagents and their therapeutic applications.