Bulletin of the Chemical Society of Japan
Online ISSN : 1348-0634
Print ISSN : 0009-2673
ISSN-L : 0009-2673
BCSJ Award Article
Delivery of Antisense Oligonucleotides to Nuclear Telomere RNA by Use of a Complex between Polysaccharide and Polynucleotide
Jusaku MinariTakanori KuboHideki OhbaNaohiko ShimadaYoich TakedaRyouji KarinagaTakahisa AnadaKazuya KoumotoTakeshi KawazuTakeshi NagasakiSeiji ShinkaiKazuo Sakurai
Author information
JOURNALS FREE ACCESS

2007 Volume 80 Issue 6 Pages 1091-1098

Details
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 importin-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.

Schizophyllan (SPG) could form a complex with antisense oligonucleotides (AS ODN). When importin-β, a nuclear transport protein was bound to SPG (through a streptavidin–biotin interaction), the complex was transported into nucleus and inhibited telomerase. Fullsize Image
Information related to the author

This article cannot obtain the latest cited-by information.

© 2007 The Chemical Society of Japan
Previous article Next article
feedback
Top