Key result
G-quadruplex formation in CpG oligonucleotides increases nuclease resistance, cellular uptake, and IL-6 production.
Why the study?
Phosphorothioate-modified CpG ODNs developed as nuclease-resistant immunotherapeutic agents cause adverse side effects, creating a need for novel CpG ODNs.
G-quadruplex formation can be used to increase the immunostimulatory activity of CpG ODNs having a natural phosphodiester backbone.
Novel PD-CpG ODNs may mitigate phosphorothioate side effects; leaves open clinical efficacy and applications pending trials.
Single-strand oligodeoxynucleotides (ODNs) containing unmethylated cytosine-phosphate-guanine (CpG) are recognized by the toll-like receptor 9, a component of the innate immunity. Therefore, they could act as immunotherapeutic agents. Chemically modified CpG ODNs containing a phosphorothioate backbone instead of phosphodiester (PD) were developed as immunotherapeutic agents resistant to nuclease degradation. However, they cause adverse side effects, and so there is a necessity to generate novel CpG ODNs. In the present study, we designed a nuclease-resistant nonmodified CpG ODN that forms G-quadruplex structures. G-quadruplex formation in CpG ODNs increased nuclease resistance and cellular uptake. The CpG ODNs designed in this study induced interleukin-6 production in a human B lymphocyte cell line and human peripheral blood mononuclear cells. These results indicate that G-quadruplex formation can be used to increase the immunostimulatory activity of CpG ODNs having a natural PD backbone.
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Hoshi et al. (2019) studied this question. Nuclease-resistant nonmodified CpG ODN that forms G-quadruplex structures was evaluated on Interleukin-6 production, nuclease resistance, and cellular uptake. G-quadruplex formation in CpG oligonucleotides increased nuclease resistance, cellular uptake, and induced interleukin-6 production in human B lymphocytes and peripheral blood mononuclear cells.
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