Cpg oligonucleotides

CpG oligonucleotides are a group of synthetically produced DNA oligonucleotides that contain a relatively high proportion of so-called CpG sequence motifs. The letter C stands for the nucleotide cytosine, p for phosphate and G for the nucleotide guanine.

The CpG sequence motif is rare in the DNA of vertebrates. Only about every 60th dinucleotide shows a CpG sequence motif. The innate immune system of vertebrates has a receptor, the toll-like receptor 9 (TLR9), which is able to recognise CpG motifs in the DNA. TLR9 is mainly expressed by lymphocytes. If a CpG motif is recognized by lymphocytes, a signaling cascade is triggered. For example, the receptor CD158k expressed on secary cells could be identified as a target structure for CpG oligonucleotides. CPG-ON cause an activation of CD158k, which leads to a dephosphorilisation of the transcription factor STAT3 and finally to apoptosis.

A single CpG sequence motif always consists of six nucleic bases, with the CG (cytosine guanosine) sequence in the middle. The two neighbouring nucleic acid bases can be arbitrary. An example of a human sequence motif is: 5'..TCGTT..3' and 5'..TCGTA...3'. In a CpG oligonucleotide this sequence (motif) is repeated several times.

The targeted activation of TLR9 by CpG oligonucleotides opens up numerous therapeutic options (e.g. improving the effect of vaccines) Further applications are seen in cancer immunotherapy, in the therapy of infectious diseases or allergic diseases.

A contrary effect to CpG oligonucleotides is caused by oligodeoxynucleotides with the TTAGGG sequence motif. They are TLR9 antagonists and have an immunosuppressive effect.

In 1984, T. Tokunaga was able to prove that the DNA fraction of Bacillus Calmette-Guérin (BCG) (BCG was administered as an adjuvant, also for the treatment of advanced malignant melanoma) was sufficient to activate NK cells (increase in interferon production; Note: after BCG therapy was abandoned, interferon therapy of malignant melanoma became the standard therapy). 10 years later, T. Tokunaga could prove that certain "palindrome sequences" (i.e. mirror-image sequences around a central dinucleotide) were responsible for this effect. Synthetically produced oligonucleotides with this motif show an analogous effect. Later it was found that a palindrome is not absolutely necessary for the immunogenic effect.

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