Abstract
Abstract Schizophyllan is a natural 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-polynucleotide is added to a schizophyllan solution, the single chain of schizophyllan forms a complex with the polynucleotide. One of the potential applications of this novel complex is an antisense-oligonucleotide (AS ODN) carrier. The present paper describes a modification technique that enables us to introduce a cholesterol group only to the side chain of schizophyllan. We prepared four cholesterol-appended schizophyllans with different modification levels. Using these compounds, we made complexes and carried out an in vitro antisense assay, administrating a phosphorothioate AS ODN to the several cell lines to depress their c-myb mRNA. When we used 2.2–2.3 mol % modified schizophyllan as the carrier, the antisense effect was most enhanced among others. The addition of β-cyclodextrin improved the complexation ability as well as the up-take for highly modified samples. Furthermore, the cytotoxicity for these modified schizophyllan samples was negligibly as small as the natural (unmodified) schizophyllan. The present work has thus clarified that schizophyllan can act as a new potential candidate for AS ODN carriers.
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