Enhancement of the antisense effect of polysaccharide-polynucleotide complexes by preventing the antisense oligonucleotide from binding to proteins in the culture medium

Schizophyllan is a β-(1 → 3)-D-glucan existing as a triple helix in water and as a single chain in dimethyl sulfoxide (DMSO), respectively. As we already reported, when a homo-phosphodiester-polynucleotide is added to the schizophyllan/DMSO solution and, subsequently, DMSO is exchanged for water, the single chain of schizophyllan (s-SPG) forms a complex with the polynucleotide. In this paper, we report that phosphorothioate oligonucleotides can form a complex with s-SPG in the same manner as phosphodiester oligonucleotides. We carried out an in vitro antisense assay combining melanoma cell lines and a phosphorothioate antisense oligonucleotide (AS ODN) to depress c-myb mRNA. We found that the AS ODN bound to the complex reduces cell growth more efficiently than that of naked AS ODN by preventing the AS ODN from binding to albumin in the culture medium and being hydrolyzed.