CpG Oligonucleotides
CpG ODN
CpG ODN with immune-stimulating effect
CpG oligonucleotides (CpG ODN) are short, single-stranded DNA sequences that contain a relatively high proportion of cytidine-guanosine-dinucleotides (CpG). These so-called CpG motifs can be found more often in bacterial and viral DNA than in vertebrate DNA. A typical CpG sequence motif consists of at least six nucleotides with a central CpG dinucleotide. The neighboring bases can be arbitrary or can also contain palindromic sequences.
Such CpG motifs are very rare in vertebrates and the cytosine is also largely in methylated form. These differences in the structure of bacterial/viral DNA and vertebrate DNA can be recognised by the immune system, which means that potential pathogens can be identified very quickly and efficiently due to their different DNA structure.
Unmethylated CpG motifs are recognised by the innate immune system of vertebrates through the Toll-like receptor 9 (TLR9). This is expressed in many immune cells and induce e.g. a strong inflammatory reaction in dendritic cells, NK cells or B lymphocytes. Likewise, CpG ODN can indirectly adapt T cell responses by releasing cytokines and induce a shift towards the Th1 immune response.
Synthetic oligonucleotides with CpG motifs can efficiently mimic the presence of bacterial or viral DNA and induce a characteristic immune response. Clinical studies have shown that activation of TLR9 by CpG motifs plays a crucial role in many medical applications. For example, the immunogenic activity of vaccines can be improved (ODN as an adjuvant), infectious and cancer diseases, as well as allergies can be alleviated, and a more effective anti-tumor response can be achieved in tumor therapy with reduced toxicity compared to cytokines.
Today, three classes of CpG ODNs (A, B and C) are mainly used, which differ in their immunostimulatory activity:
Class A: This class is characterised by a central CpG-bearing palindromic motif and a polyG stretch at the 3´ end with PTO connections, which protects against unspecific degradation. Class A CpG ODN strongly stimulate IFN-α production, but are only weak stimulators of TLR9-dependent NF-κB signal transmission.
Class B: Class B CpG ODN carry a full PTO backbone with one or more CpG dinucleotides. They can activate B cells extremely effectively, but only very weakly the IFN-α secretion.
Class C: Class C combines the properties of both classes. They have both a full PTO backbone and a CpG-containing palindromic motif in the middle of the sequence. This class activates IFN-α production as well as B-cell stimulation.
| CpG ODN | Sequence | Class |
|---|---|---|
| CpG ODN 1826 | t*c*c*a*t*g*a*c*g*t*t*c*c*t*g*a*c*g*t*t | B |
| CpG ODN 2006 | t*c*g*t*c*g*t*t*t*t*g*t*c*g*t*t*t*t*g*t*c*g*t*t | B |
All CpG oligonucleotides can be easily ordered through our web ordering system. Please simply enter the desired sequence in the corresponding field in the order form. PTO (phosphorothioates) are symbolised with an asterisk * in the sequence. Alternatively, you can also order using the Excel order form. Simply send us the completed Excel form to order@biomers.net.
Literature:
1) Immune effects and therapeutic applications of CpG motifs in bacterial DNA. Krieg AM, Kline JN; Immunopharmacology 48 (2000), 303–305.
2) Synthetic CpG-ODN rapidly enriches immune compartments in neonatal chicks to induce protective immunity against bacterial infections. Gunawardana T, Ahmed KA, Goonewardene K, Popowich S, Kurukulasuriya S, Karunarathna R, Gupta A, Lockerbie B, Foldvari M, Tikoo SK, Willson P, Gomis S; Scientific Reports volume 9 (2019), Article number: 341.
3) C-Class CpG ODN: sequence requirements and characterization of immunostimulatory activities on mRNA level. Jurk M, Schulte B, Kritzler A, Noll B, Uhlmann E, Wader T, Schetter C, Krieg AM, Vollmer J; Immunobiology (2004), 209(1-2):141-54.
4) Immunostimulatory Activities of CpG-Oligodeoxynucleotides in Teleosts: Toll-Like Receptors 9 and 21. Lai C-Y, Yu G-Y, Luo Y, Xiang R, Chuang T-H; Front. Immunol. (2019), https://doi.org/10.3389/fimmu.2019.00179.
5) Immunotherapeutic uses of CpG oligodeoxynucleotides. Klinman DM; Nature Reviews Immunology (2004), volume 4, pages249–259.
6) CpG DNA as a vaccine adjuvant. Bode C, Zhao G, Steinhagen F, Kinjo T, Klinman DM; Expert Rev Vaccines (2011); 10(4): 499–511.
