Transferrin-appended β-(1→3)-D-glucan schizophyllan for antisense oligonucleotides delivery to enhance the cellular uptake

Takahisa Anada; Ryouji Karinaga; Masami Mizu; Kazuya Koumoto; Takahiro Matsumoto; Munenori Numata; Seiji Shinkai; Kazuo Sakurai

doi:10.1380/ejssnt.2005.195

Regular Papers

Transferrin-appended β-(1→3)-D-glucan schizophyllan for antisense oligonucleotides delivery to enhance the cellular uptake

Takahisa Anada, Ryouji Karinaga, Masami Mizu, Kazuya Koumoto, Takahiro Matsumoto, Munenori Numata, Seiji Shinkai, Kazuo Sakurai

Author information

Takahisa Anada
Department of Chemical Process & Environments, The University of Kitakyushu, Japan
Ryouji Karinaga
Department of Chemical Process & Environments, The University of Kitakyushu, Japan
Masami Mizu
Department of Chemical Process & Environments, The University of Kitakyushu, Japan
Kazuya Koumoto
Department of Chemical Process & Environments, The University of Kitakyushu, Japan
Takahiro Matsumoto
Faculty of Engineering, Department of Chemistry & Biochemistry, Graduate School of Engineering, Kyushu University, Japan
Munenori Numata
Faculty of Engineering, Department of Chemistry & Biochemistry, Graduate School of Engineering, Kyushu University, Japan
Seiji Shinkai
Faculty of Engineering, Department of Chemistry & Biochemistry, Graduate School of Engineering, Kyushu University, Japan
Kazuo Sakurai
Department of Chemical Process & Environments, The University of Kitakyushu, Japan

Keywords: Biological molecules - nucleic acids, Biological molecules - proteins, Biological compounds, Compound formation, Biological aspects of nano-structures

JOURNAL FREE ACCESS

2005 Volume 3 Pages 195-202

DOI https://doi.org/10.1380/ejssnt.2005.195

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Abstract

Schizophyllan (SPG) is a natural β-(1→3)-D-glucan existing as a triple helix in water and as a single chain in dimethylsulfoxide (DMSO), respectively. As we already reported, when a homo-phosphodiester polynucleotide [for example, poly(dA) or poly(C)] is added to the SPG/DMSO solution and subsequently DMSO is exchanged for water, SPG 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 which enables us to introduce transferrin to the reducing end of SPG (Tf-SPG). We made a complex from Tf-SPG and AS ODN and carried out an in vitro antisense assay. We found that Tf-SPG dramatically enhances the antisense effect. Their superiority can be ascribed to enhancement of endocytosis due to the attached transferrin. One of the peculiar features of our system is that the complex (i.e., carrier + AS ODN) is charged negatively in total, because SPG itself is a neutral polysaccharide. This feature is different from the conventional systems such as cationic liposomes and polycations. The present work has thus clarified that SPG can act as a new potential candidate for AS ODN carriers. [DOI: 10.1380/ejssnt.2005.195]

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