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

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2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1091-1098
Number of pages8
JournalBulletin of the Chemical Society of Japan
Volume80
Issue number6
DOIs
Publication statusPublished - 2007 Dec 1

ASJC Scopus subject areas

  • Chemistry(all)

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    Minari, J., Kubo, T., Ohba, H., Shimada, N., Takeda, Y., Karinaga, R., Anada, T., Koumoto, K., Kawazu, T., Nagasaki, T., Shinkai, S., & Sakurai, K. (2007). Delivery of antisense oligonucleotides to nuclear telomere RNA by use of a complex between polysaccharide and polynucleotide. Bulletin of the Chemical Society of Japan, 80(6), 1091-1098. https://doi.org/10.1246/bcsj.80.1091