CpG Oligodeoxynucleotide

CpG oligonucleotides, as a CpG - oligodeoxynucleotide ( CpG ODN) referred to are a class of single-stranded synthetic DNA oligonucleotides, which contain a relatively high content of CpG motifs.

Description

The CpG sequence motif is under-represented in the DNA of vertebrates. Just about every sixtieth dinucleotide CpG is of type. The letter C stands for the nucleotide cytosine, the p for phosphate and G for guanine nucleotide. In vertebrates, the cytosine of the CpG motifs located 60 to 90 percent before in methylated form. In the genome of bacteria and viruses is statistically every sixteenth dinucleotide type CpG and cytosine is largely present in a non -methylated form. The innate immune system of vertebrates has with the Toll-like receptor 9 via a receptor, the CpG motifs in the DNA is able to recognize. The protein TLR9 is mainly expressed by certain leukocytes., A CpG motif of this protein-DNA interaction is detected, a signaling cascade is triggered. A single CpG sequence motif consists of six nucleobases, which stands in the middle of the CG sequence and the two neighboring nucleobases can be arbitrary. example:

In a CpG oligonucleotide this motif is repeated several times. The two most effective human motives are:

While in mice the subject

Is particularly effective.

Potential applications

The selective activation of TLR9 by CpG oligonucleotides opens up many possibilities for the use of these compounds for example, vaccines to enhance their effect. First clinical trials for use as an adjuvant have so far been promising. Furthermore, potential in the field of cancer immunotherapy to combat infectious diseases, and allergies are seen. In tumor therapy, one hopes that - in comparison to the administration of cytokines - effective anti - tumor responses with reduced toxicity.

The opposite of CpG - oligonucleotides cause oligodeoxynucleotides with the TTAGGG motif, which has an immunosuppressive effect by endogenous DNA (self - DNA) is imitated. The motif TTAGGG repeats in the telomeres of vertebrates from 5 'to 3'. The gift of synthetic TTAGGG Oligodesoxynuklide ( TTAGGG ODN), for example, anti-inflammatory. These compounds are TLR9 antagonists.

History

In 1984 it established a working group to the Japanese T. Tokunaga that the DNA fraction of Bacillus Calmette- Guérin (BCG ), a well-known since the late 19th century Adjuvants, sufficient to activate NK cells and interferon production to increase. In comparison, the DNA of other vertebrates was not in a position. The same group identified in 1994 that so-called palindromic, that is mirror-image sequences around a central dinucleotide, with cytosine and guanine in the middle, were responsible for this effect and synthetic oligonucleotides can show with this design a similar effect. The American Arthur M. Krieg from the Veterans Affairs Medical Center in Iowa City, and colleagues presented in 1995 found that a palindrome for the immunogenic effect is not absolutely necessary. The working group of war found the first time that these motifs in murine B- lymphocytes, both in vitro and in vivo, their proliferation, and stimulates the secretion of antibodies. In this immunogenic effect a possible evolutionary link between the immune system of vertebrates, in the detection of DNA of pathogenic origin, and the suppression of the CpG motif in its own DNA has been proposed. The potential application as an adjuvant described the authors in their publication.

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