Nanotech 2011

Novel CpG oligodeoxynucleotide and its delivery system

T. Yamazaki, W. Meng W, C. Zhi, Y. Zhu, N. Hanagata
National Institute for Materials Science (NIMS), JP

Keywords: Toll-like receptor 9, CpG, TH1-type immune response,mesoporous silica, boronitride

Abstract:

Short single-stranded synthetic oligodeoxynucleotides with CpG motifs (CpG ODNs) can induce TH1-type immune response by interacting with toll-like receptor 9 (TLR9), are thought to be potential immuno-therapeutic adjuvant for various diseases such as cancer, asthma, pollinosis, and infectious diseases. However, application of the unmodified natural CpG ODN to immunotherapy has been notably limited by its extreme susceptibility to nuclease degradation. Chemical modification, such as substitution of the phosphodiester linkage with a phosphorothioate (PTO), is one of the most effective and reliable methods for increasing the biological activity of CpG ODNs, due to increase the resistance to enzymatic degradation. However, ODNs with a PTO backbone lead to side effects such as unspecific binding to various proteins and renal damage. Therefore it is still challanging to develop suitable ODNs for therapy. In this study, we first report our new CpG ODNs, is able to resist nuclease degradation and acted as effective activatior of hTLR9. We also report our novel nano-particles, amino-modified mesoporous silica, and boronitride as natural CpG ODN carriers. These carriers increased the immuno-stimulatory activity of natural CpG ODNs, through increase in the uptake of CpG ODNs by lysosomes and enhancement of stability against nuclease degradation.
 

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