Preparation of the lyophilizable DNA complexes and novel therapeutic system with the freeze-dried solid complexes

• Project/Area Number: 19510119
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nanomaterials/Nanobioscience
• Research Institution: Otsuma Women's University
• Principal Investigator: KOYAMA Yoshiyuki Otsuma Women's University, 家政学部, 教授 (00162090)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 核酸 / ナノバイオ / バイオテクノロジー / 遺伝子治療 / 凍結乾燥 / 癌治療 / 非ウィルスベクター

Research Abstract

ヒアルロン酸でコートしたDNA/ポリカチオン複合体は、凍結乾燥後も活性が維持された。そこで、極低濃度で調製した微小な複合体を凍結乾燥し、少量の水を加えることで、これまで不可能とされていた極微小なDNA 複合体超微粒子の高濃度分散液の調製に成功した
GM-CSF遺伝子をコードしたプラスミドを用いて極微小な複合体を調製し、担癌マウスの腫瘍局所内に投与したところ、ほとんどのマウスで腫瘍の完全消失が見られた

Research Products

• [Journal Article] Efficient in vivo Gene Transfection by Stable DNA/PEI Complexes Coated by Hyaluronic Acid (2008)
  • Author(s): T. Ito, N. I.-Tanaka, Y. Koyama
  • Journal Title: J. Drug Targeting 16 Pages: 276-281
  • Peer Reviewed
• [Journal Article] Highly efficient in vivo gene transfection by plasmid/PEI complexes coated by anionic PEG derivatives bearing carboxyl groups and RGD peptide (2008)
  • Author(s): M. Sakae, T. Ito, C. Yoshihara, N. I.-Tanaka, H. Yanagie, M. Eriguchi, Y. Koyama
  • Journal Title: Biomedicine & Pharmacotherapy 62 Pages: 448-453
  • Peer Reviewed
• [Journal Article] In Vitro Gene Delivery by pDNA/Chitosan Complexes Coated with Anionic PEG Derivatives that Have a Sugar Side Chain (2008)
  • Author(s): M. Hashimoto, Y. Koyama, T. Sato
  • Journal Title: Chem. Lett. 37 Pages: 266-267
  • NAID: 10021078166
  • Peer Reviewed
• [Journal Article] Preparation of Fine DNA Particles and High Level Tumor-targeted In Vivo Gene Expression after Intravenous Injection (2008)
  • Author(s): T. Ito, M. Otsuka, Y. Koyama
  • Journal Title: Molecular Therapy 16
  • Peer Reviewed
• [Journal Article] Efficient in vivo Gene Transfection by Stable DNA/PEI Complexes Coated by Hyaluronic Acid (2008)
  • Author(s): T. Ito
  • Journal Title: J. Drug Targeting 16 Pages: 276-281
  • Peer Reviewed
• [Journal Article] Highly efficient in vivo gene transfection by plasmid/PEI complexes coated by anionic PEG derivatives bearingcarboxyl groups and RGD peptide (2008)
  • Author(s): M. Sakae
  • Journal Title: Biomedicine & Pharmacotherapy 62 Pages: 448-453
  • Peer Reviewed
• [Journal Article] In Vitro Gene Delivery by pDNA/Chitosan Complexes Coated with Anionic PEG Derivative that Have a Sugar Side Chain (2008)
  • Author(s): H. Hashimoto
  • Journal Title: Chem. Lett. 37 Pages: 266-267
  • Peer Reviewed
• [Journal Article] Efficient in vivo Gene Transfection by Stable DNA/PEI Complexes Coated by Hyaluronic Acid (2008)
  • Author(s): Tomoko Ito
  • Journal Title: Journal of Drug Targeting (in press)
  • Peer Reviewed
• [Journal Article] Highly efficient in vivo gene transfection by plasmid/PEI complexes coated by anionic PEG derivatives bearing carboxyl groups and RGD peptide (2008)
  • Author(s): Mitsuko Sakae
  • Journal Title: Biomedicine&Pharmacotherapy (in press)
  • Peer Reviewed
• [Journal Article] Dissociation of DNA-polycation complexes by polyanions and polyampholytes (2007)
  • Author(s): Chwen-Yang Shew
  • Journal Title: Chemical Physics Letters 446 Pages: 59-64
  • Peer Reviewed
• [Presentation] Preparation of Very Small Plasmid Complex Particles and Their Therapeutic Effects against Cancer (2009)
  • Author(s): Y. Koyama, C. Yoshihara, K. Hamada, T. Ito
  • Organizer: Gordon Research Conference
  • Place of Presentation: Ventura (CA)
• [Presentation] Improve of transcription-and transfection efficiency by synthetic polyampholytes (2009)
  • Author(s): polyampholytes, C. Yoshihara, T. Ito, C.-Y. Shew, Y. Koyama
  • Organizer: Gordon Research Conference
  • Place of Presentation: Ventura (CA)
• [Presentation] Analysis of the surface structure of DNA/polycation/hyaluronic acid ternary complex by Raman microscopy (2009)
  • Author(s): T. Ito, Y. Koyama, M. Otsuka
  • Organizer: Gordon Research Conference
  • Place of Presentation: Ventura (CA)
• [Presentation] 極微細なプラスミド複合体の調製とその治療効果 (2009)
  • Author(s): 小山義之, 濱田雄行, 伊藤智子, 芳原智恵子
  • Organizer: アンチセンスシンポジウム
  • Place of Presentation: 岐阜
• [Presentation] DNA/ポリカチオン/両性イオン高分子三元複合体の調製条件と転写活性との相関 (2009)
  • Author(s): 芳原智恵子, C.-Y. Shew, 小山義之
  • Organizer: アンチセンスシンポジウム
  • Place of Presentation: 岐阜
• [Presentation] Preparation of Very Small Plasmid Complex Particles and Their Therapeutic Effects against Cancer (2009)
  • Author(s): Y. Koyama, C. Yoshihara, K. Hamada, T. Ito
  • Organizer: Gordon Research Conference
  • Place of Presentation: Ventura (CA), USA
• [Presentation] Improve of transcription-and transfection efficiency by synthetic polyampholytes (2009)
  • Author(s): C. Yoshihara, T. Ito, C. -Y. Shew, Y, Koyama
  • Organizer: Gordon Research Conference
  • Place of Presentation: Ventura (CA), USA
• [Presentation] Analysis of the surface structure of DNA/polycation/hyaluronic acid ternary complex by Raman microscopy (2009)
  • Author(s): T. Ito, Y. Koyama, M. Otsuka
  • Organizer: Gordon Research Conference
  • Place of Presentation: Ventura (CA), USA
• [Presentation] レーザーラマン顕微鏡によるDNA/ポリカチオン/ヒアルロン酸三元複合体の表面構造解析 (2008)
  • Author(s): 伊藤智子, 小山義之, 大塚誠
  • Organizer: 日本バイオマテリアル学会シンポジウム2008
  • Place of Presentation: 東京
• [Presentation] Improve of transcription- and transfection-efficiency by synthetic polyampholytes (2008)
  • Author(s): C. Yoshihara, T. Ito, C.-Y. Shew, Y. Koyama
  • Organizer: 国際核酸シンポジウム
  • Place of Presentation: 京都
• [Presentation] DNA/ポリカチオン/ポリアニオン/両性イオン型高分子四元複合体による高発現遺伝子導入システム (2008)
  • Author(s): 芳原智恵子, 伊藤智子, 小山義之
  • Organizer: 第24回DDS学会
  • Place of Presentation: 東京
• [Presentation] 極微細なプラスミド複合体の調製とその治癒効果 (2008)
  • Author(s): 小山義之, 濱田雄行, 伊藤智子, 芳原智恵
  • Organizer: 第24回DDS学会
  • Place of Presentation: 東京
• [Presentation] Preparation of Fine DNA Particles and High Level Tumor-targeted In Vivo Gene Expression after Intravenous Injection (2008)
  • Author(s): Injection, T. Ito, M. Otsuka, Y. Koyama
  • Organizer: アメリカ遺伝子治療学会
  • Place of Presentation: Boston (MA)
• [Presentation] 合成両イオン型高分子による転写・翻訳促進機構 (2008)
  • Author(s): 芳原智恵子, 伊藤智子, 小山義之
  • Organizer: 第9回遺伝子・デリバリー研究会シンポジウム
  • Place of Presentation: 大阪
• [Presentation] 極微細なプラスミド複合体の調製とその治療効果 (2008)
  • Author(s): 小山義之, 清田雄行, 伊藤智子, 芳原智恵子
  • Organizer: アンチセンスシンポジウム
  • Place of Presentation: 岐阜
• [Presentation] DNA/ポリカチオン/両性イオン高分子三元複合体の調製条件と転写活性との相関 (2008)
  • Author(s): 芳原智恵子, C. -Y. Shew, 小山義之
  • Organizer: アンチセンスシンポジウム
  • Place of Presentation: 岐阜
• [Presentation] DNA/ポリカチオン/ポリアニオン/両性イオン型高分子四元複合体による高発現遺伝子導入システム (2008)
  • Author(s): 芳原智恵子, 伊藤智子, 小山義之
  • Organizer: 第24回日本DDS学会
  • Place of Presentation: 東京
• [Presentation] 極微細なプラスミド複合体の調製とその治癒効果 (2008)
  • Author(s): 小山義之, 濱田雄行, 伊藤智子, 芳原智恵子
  • Organizer: 第24回日本DDS学会
  • Place of Presentation: 東京
• [Presentation] Preparation of Fine DNA Particles and High Level Tumor-targeted In Vivo Gene Expression after intravenous Injection (2008)
  • Author(s): T. Ito
  • Organizer: 11th Annual Meething of the American Society of Gene Therapy
  • Place of Presentation: Boston, Massachusetts. USA
• [Presentation] In Vivo Efficient Gene Expression by Freeze-Dried DNA Complexes Coated by Polyanions (2007)
  • Author(s): Tomoko Ito, Keiko Abe, Naoko Iida-Tanaka, Yoshiyuki Koyama
  • Organizer: American Society of Gene Therapy
  • Place of Presentation: シアトル、アメリカ合衆国
  • Year and Date: 2007-06-02