Delivery of antisense DNA to nuclear telomere RNA by use of a natural polysaccharide of schizophyllan

PMSE 568

Jusaku Minari, m56115@env.kitakyu-u.ac.jp1, Takanori OhbaKubo, h.ooba@aist.go.jp2, Naohiko Shimada, shimada@env.kitakyu-u.ac.jp3, Yoichi Takeda, takeda@env.kitakyu-u.ac.jp3, Takeshi Nagasaki, nagasaki@bioa.eng.osaka-cu.ac.jp4, Seiji Shinkai5, and Kazuo Sakurai, sakurai@env.kitakyu-u.ac.jp3. (1) Department of Chemical Processes & Environments, The University of Kitakyushu, 1-1, Hibikino, Wakamatu-ku, Kitakyushu, 808-0135, Japan, (2) Single-Molecule Bioanalysis Laboratoty, National Institute for Advanced Industrial Science and Technology, 807-1 Shukumachi Tosu Saga Japan, 841-0052, Japan, (3) Department of Chemical Processes and Environments, The University of Kitakyushu, 1-1, Hibikino, Wakamatu-ku, Kitakyushu, 808-0135, Japan, (4) Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka, 5588585, Japan, (5) Graduate School of Engineering, Kyushu University, Fukuoka, 819-0395, Japan
Telomerase can be a target for anti-cancer therapy and antisense oligonucleotides (ODNs) have to be delivered into cellular nucleus, because the target telomerase is present in nucleus. The present work shows a new strategy to deliver ODN to nucleus by use of novel complex made from a natural polysaccharide schizophyllan (SPG) and ODNs. Nuclear transport is strictly regulated by the nuclear pour size and related proteins. The smaller molecular weight has the better chance to be transported; however, the complex stability is decreased with decreasing the molecular weight. We optimized the suitable molecular weight to be 25K. Furthermore, we attached importin-beta 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 naked dose.
 

Advances in Protein Drugs and Gene Delivery: Delivery and Diagnostic Technologies
8:30 AM-12:00 PM, Thursday, 14 September 2006 San Francisco Marriott -- Salon 7, Oral

Division of Polymeric Materials: Science & Engineering

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006