Delivery of antisense oligonucleotides to nuclear telomere RNA by use of a complex between polysaccharide and polynucleotide

Jusaku Minari, Takanori Kubo, Hideki Ohba, Naohiko Shimada, Yoich Takeda, Ryouji Karinaga, Takahisa Anada, Kazuya Koumoto, Takeshi Kawazu, Takeshi Nagasaki, Seiji Shinkai, Kazuo Sakurai

研究成果: Contribution to journalArticle査読

3 被引用数 (Scopus)

抄録

Telomerase, which is highly activated in neoplastic cells, can be a target for antisense therapy, and for that purpose, antisense oligonucleotides (AS ODNs) have to be effectively delivered into cellular nucleus where the target telomerase is present. The present work shows a new strategy to deliver AS ODNs to nucleus by use of a novel complex made from a natural polysaccharide schizophyllan (SPG) and AS ODNs. Nuclear transport is strictly regulated by the nuclear pore size and the related proteins. If the molecular weight of SPG is decreased, the SPG/AS ODN complex should be easily transported, although the stability of the complex decreases with a decrease in the molecular weight. We optimized the molecular weight of SPG to be 25 K. Furthermore, we attached importing-β (a nuclear transport protein) to the side chain of SPG by use of a streptavidin-biotin interaction. When this complex was added to Jurkat cells, the telomerase activity was more suppressed than the naked dose, indicating that the importin-β in the complex induced the nuclear transport of the complexed AS ODN and the AS ODN inhibited the telomerase. The present work shows a new methodology for nuclear anti-sense therapy that should be important in future anti-cancer therapies.

本文言語英語
ページ(範囲)1091-1098
ページ数8
ジャーナルBulletin of the Chemical Society of Japan
80
6
DOI
出版ステータス出版済み - 2007

All Science Journal Classification (ASJC) codes

  • 化学 (全般)

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