A polysaccharide carrier for immunostimulatory CpG DNAs to enhance cytokine secretion

A β-(1→3)-D-glucan schizophyllan (SPG) forms a stoichiometric complex with some polynucleotides. This paper describes our attempt to apply the SPG complex to deliver CpG DNA to endosome in order to enhance cytokine secretion. To increase cellular up-take, we introduced spermine, arginine-glycine-aspartic acid tripeptide, octaarginine, or cholesterol to the SPG side chain. The chemically modified SPG shows essentially no-cytotoxicity. When CpG DMA complex made therefrom was exposed to macrophages, dramatic enhancement in the cytokine secretion was observed. It increased 5-10 times from the naked dose, and 100 times from the background. This performance promises that SPG can be an excellent carrier for CpG DNA. The paper will include a recent result for in-vivo assay carried out by Profs. Akira and Ishii at Osaka Univ.