Finding a novel beta-(1→3)-D-Glucan/polynucleotide complex and its applications for an immunocyte-targeting delivery

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 certain polynucleotides. 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 including dendritic immune cells express a receptor called Dectin-1. We have demonstrated that Dectin-1 recognizes SPG/oligonucleotide (ODN) complexes, and the complex is eventually ingested by the cells. This finding suggests that SPG/ODN complex can be specifically ingested by activated immunocytes and the bound ODN can exert its effect after ingestion. The present review 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 (AS)-ODN, CpG-ODN, and siRNA to antigen presenting cells (APCs) to cure the diseases due to disorientation of immune.