Oligonucleotides (ODNs) are easily decomposed in biological fluids, which makes it difficult to administrate antisense DNA or CpG motif in naked state. Cationic compounds have been used as a carrier for ODNs; however, they have drawbacks in cytotoxicity and selectivity in cellular or organ targeting. Schizophyllan (SPG) is a natural beta-(1→3)-D-glucan existing as a triple helix in water and as a single chain in alkaline solutions, respectively. When homo-polynucleotides such as poly(dA) are added to SPG alkaline solution and subsequently pH is adjusted to be neutral, the single chain of SPG forms a stoichiometric complex with the polynucleotide. The complex can protect the bound DNA against nuclease-mediated hydrolysis or non-specific binding to serum proteins. Furthermore, recent immunology revealed that activated antigen presenting cells (APCs) including dendritic immune cells express a receptor called Dectin-1. We have demonstrated that Dectin-1 recognizes SPG/ODN complexes, and the complex is eventually ingested by APCs. This finding suggests that SPG/ODN complex can be specifically ingested by activated APCs and the bond ODN can exert its effect after ingestion. The present talk will show our recent in-vivo and vitro studies to prove this idea and provide a new strategy to specifically transport functional ODNs including antisense-DNA, CpG-DNA, and siRNA to APCs to cure the diseases due to disorientation of immune.

Beta-glucan for therapeutic functional oligonucleotides: Immunocyte targeting DDS with dectin-1

253rd National Meeting (2017)

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