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 language | English |
|---|---|
| Pages (from-to) | 1091-1098 |
| Number of pages | 8 |
| Journal | Bulletin of the Chemical Society of Japan |
| Volume | 80 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Dec 1 2007 |
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All Science Journal Classification (ASJC) codes
- Chemistry(all)
Cite this
Delivery of antisense oligonucleotides to nuclear telomere RNA by use of a complex between polysaccharide and polynucleotide. / Minari, Jusaku; Kubo, Takanori; Ohba, Hideki; Shimada, Naohiko; Takeda, Yoich; Karinaga, Ryouji; Anada, Takahisa; Koumoto, Kazuya; Kawazu, Takeshi; Nagasaki, Takeshi; Shinkai, Seiji; Sakurai, Kazuo.
In: Bulletin of the Chemical Society of Japan, Vol. 80, No. 6, 01.12.2007, p. 1091-1098.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Delivery of antisense oligonucleotides to nuclear telomere RNA by use of a complex between polysaccharide and polynucleotide
AU - Minari, Jusaku
AU - Kubo, Takanori
AU - Ohba, Hideki
AU - Shimada, Naohiko
AU - Takeda, Yoich
AU - Karinaga, Ryouji
AU - Anada, Takahisa
AU - Koumoto, Kazuya
AU - Kawazu, Takeshi
AU - Nagasaki, Takeshi
AU - Shinkai, Seiji
AU - Sakurai, Kazuo
PY - 2007/12/1
Y1 - 2007/12/1
N2 - 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.
AB - 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.
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U2 - 10.1246/bcsj.80.1091
DO - 10.1246/bcsj.80.1091
M3 - Article
AN - SCOPUS:58149310777
VL - 80
SP - 1091
EP - 1098
JO - Bulletin of the Chemical Society of Japan
JF - Bulletin of the Chemical Society of Japan
SN - 0009-2673
IS - 6
ER -