Oligonucleotides (ODNs) are easily hydrolyzed in biological fluids, which makes difficult to administrate antisense DNA or CpG motif in the naked state. Polyethylenimine or cationic lipids have been used as a carrier for those oligonucleotides, however, they have drawbacks in cytotoxicity and compaction. Schizophyllan (SPG) is a natural b-(1?3)-D-glucan existing as a triple helix in water and as a single chain in dimethylsulfoxide (DMSO), respectively. When some homo-polynucleotide is added to the SPG/DMSO solution and subsequently DMSO is exchanged for water, the single chain of SPG forms a complex with the polynucleotide. The complex can protect the bound DNA against nuclease-mediated hydrolysis or non-specific binding to serum proteins. We have showed that these characteristics make possible to use native phosphodiester DNAs for antisense therapy. Furthermore, recent immunology revealed that activated antigen presenting cells (APCs) can express a receptor called Dectin-1 on their surface and Dectin-1 recognizes SPG and thus 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 system. 1.         Enhanced Cytokine Secretion Owing to Multiple CpG Side Chains of DNA Duplex. Oligonucleotides.; 18(4); 337-344 (2008)2.         Encapsulation of a Hydrophobic Drug into a Polymer-Micelle Core Explored with Synchrotron SAXS. Langmuir, 26, 7544-7551(2010)3.         Plasmacytoid Dendritic Cells Delineate Immunogenicity of Influenza Vaccine Subtypes. Science, Transl. Med 3 25

Novel polysaccharide carrier for functional oligonucleotides: APS targeting DDS with Dectin-1

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.