Development of novel gene therapy targeting age-related macular degeneration

• Project/Area Number: 23659813
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Nagasaki University
• Principal Investigator: SASAKI Hitoshi 長崎大学, 大学病院, 教授 (00170689)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 加齢黄斑変性症 / 遺伝子治療 / 遺伝子デリバリー / γ-polyglutamic acid

Research Abstract

In this study, we developed the safe and efficient novel ocular gene delivery system to the age-related macular degeneration. We successfully prepared the stable nanoparticles (pDNA-PEI complex: PEI complex, pDNA-PEI-gamma-PGA complex: PGA complex, pDNA-PEI-CS complex: CS complex) by optimization of the mix ratio. The PGA complex and CS complex showed high gene expression comparable to PEI complex. While PEI complex showed severe agglutination of vitreous body and cytotoxicity, PGA complex and CS complex showed no agglutination of vitreous body and no cytotoxicity. We also developed siRNA-PEI-gamma-PGA (siPGA complexes). The siPGA complexes showed high silencing effect comparable to commercial vector (lipofectamine) without cytotoxicity.

Research Products

• [Journal Article] Secure splenic delivery of plasmid DNA and its application to DNA vaccine (2013)
  • Author(s): Kurosaki T, Kodama Y, Muro T, Higuchi N, Nakamura T, Kitahara T, Miyakoda M, Yui K, Sasaki H
  • Journal Title: Biol Pharm Bull Volume: 36(11) Pages: 1800-6
  • NAID: 130003382044
  • Peer Reviewed
• [Journal Article] Ternary complex of plasmid DNA with protamine and γ-polyglutamic acid for biocompatible gene delivery system (2013)
  • Author(s): Kanda K, Kodama Y, Kurosaki T, Imamura M, Nakagawa H, Muro T, Higuchi N, Nakamura T, Kitahara T, Honda M, Sasaki H
  • Journal Title: Biol Pharm Bull Volume: 36(11) Pages: 1794-9
  • NAID: 130003382043
  • Peer Reviewed
• [Journal Article] Ocular gene delivery systems using ternary complexes of plasmid DNA, polyethylenimine, and anionic polymers (2013)
  • Author(s): Kurosaki T, Uematsu M, Shimoda K, Suzuma K, Nakai M, Nakamura T, Kitahara T, Kitaoka T, Sasaki H
  • Journal Title: Biol Pharm Bull Volume: 36(1) Pages: 96-101
  • NAID: 130003361352
  • Peer Reviewed
• [Journal Article] Ternary Complex of Plasmid DNA with Protamine and γ-Polyglutamic Acid for Biocompatible Gene Delivery System (2013)
  • Author(s): Kosuke Kanda, Yukinobu Kodama, Tomoaki Kurosaki, Masanobu Imamura, Hiroo Nakagawa, Takahiro Muro, Norihide Higuchi, Tadahiro Nakamura, Takashi Kitahara, Masayuki Honda, Hitoshi Sasaki
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 36 Pages: 1794-1799
  • NAID: 130003382043
  • Peer Reviewed
• [Journal Article] Ocular Gene Delivery Systems Using Ternary Complexes of Plasmid DNA, Polyethylenimine, and Anionic Polymers (2013)
  • Author(s): Kurosaki T, Uematsu M, Shimoda K, Suzuma K, Nakai M, Nakamura T, Kitahara T, Kitaoka T, Sasaki H.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 36 Issue: 1 Pages: 96-101
  • DOI: 10.1248/bpb.b12-00728
  • NAID: 130003361352
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] Self-assemble gene delivery system for molecular targeting using nucleic acid aptamer (2012)
  • Author(s): Kurosaki T, Higuchi N, Kawakami S, Higuchi Y, Nakamura T, Kitahara T, Hashida M, Sasaki H
  • Journal Title: Gene Volume: 491(2) Pages: 205-9
  • NAID: 120006985259
  • Peer Reviewed
• [Journal Article] Secure and effective gene vector of polyamidoamine dendrimer pharmaceutically modified with anionic polymer (2011)
  • Author(s): Kurosaki T, Yamashita Y, Aki K, Harasawa H, Nakagawa H, Kodama Y, Higuchi N, Nakamura T, Kitahara T, Sasaki H
  • Journal Title: J Pharm Sci Volume: 100(11) Pages: 4855-63
  • Peer Reviewed
• [Journal Article] Nanoparticles electrostatically coated with folic acid for effective gene therapy (2011)
  • Author(s): Kurosaki T, Morishita T, Kodama Y, Sato K, Nakagawa H, Higuchi N, Nakamura T, Hamamoto T, Sasaki H, Kitahara T
  • Journal Title: Mol Pharm Volume: 8(3) Pages: 913-9
  • Peer Reviewed
• [Presentation] 樹状細胞標的型ナノデバイスを用いたマラリアDNA ナノワクチンの開発 (2013)
  • Author(s): 西垣 和香、兒玉 幸修、北原 隆志、佐々木 均
  • Organizer: 第30回日本薬学会九州支部大会
  • Place of Presentation: 佐世保
  • Year and Date: 2013-12-08
• [Presentation] Dendrigraft poly-L-lysine を用いた生体内分解型遺伝子ベクターの開発 (2013)
  • Author(s): 塩川 裕美、兒玉 幸修、北原 隆志、佐々木 均
  • Organizer: 日本薬剤学会第28年会
  • Place of Presentation: 名古屋
  • Year and Date: 2013-05-25
• [Presentation] ポリヌクレオチド被膜型複合体による脾臓指向性新規遺伝子ベクターの開発 (2013)
  • Author(s): 矢次 結衣子、兒玉 幸修、大久保 智佳子、北原 隆志、佐々木 均
  • Organizer: 日本薬剤学会第28年会
  • Place of Presentation: 名古屋
  • Year and Date: 2013-05-25
• [Presentation] Fetuin 被膜型複合体による新規遺伝子ベクターの構築 (2013)
  • Author(s): 兒玉 幸修、北原 隆志、江頭 かの子、中嶋 幹郎、樋口 則英、中村 忠博、佐々木 均
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-28
• [Presentation] 静電的自己組織化を基盤としたアニオン性siRNA ベクターの開発 (2012)
  • Author(s): 塩川 裕美、兒玉 幸修、原内 智慧、北原 隆志、佐々木 均
  • Organizer: 第29回日本薬学会九州支部大会
  • Place of Presentation: 熊本
  • Year and Date: 2012-12-08
• [Presentation] 安全かつ効果的な眼疾患用新規遺伝子ベクターの開発 (2012)
  • Author(s): 佐々木 均、兒玉 幸修、黑﨑 友亮、樋口 則英、北原 隆志、中村 忠博
  • Organizer: 第32回日本眼薬理学会
  • Place of Presentation: 滋賀
  • Year and Date: 2012-09-15
• [Presentation] ホスファチジルセリンアナログを用いた脾臓指向性遺伝子導入ベクターの開発 (2012)
  • Author(s): 大久保 智佳子、仲宗根 ちひろ、黒崎 友亮、兒玉 幸修、北原 隆志、佐々木 均
  • Organizer: 日本薬剤学会第27年会
  • Place of Presentation: 神戸
  • Year and Date: 2012-05-24
• [Presentation] 肝細胞選択的なグリチルリチン含有遺伝子ベクターの開発 (2012)
  • Author(s): 原内 智慧、川鍋 早紀、黒崎 友亮、兒玉 幸修、北原 隆志、佐々木 均
  • Organizer: 日本薬剤学会第27年会
  • Place of Presentation: 神戸
  • Year and Date: 2012-05-24
• [Presentation] 制癌剤と遺伝子同時送達を目的としたメトトレキサート被膜型遺伝子ベクターの開発 (2012)
  • Author(s): 兒玉 幸修、黒崎 友亮、江頭 かの子、中嶋 幹郎、中川 博雄、樋口 則英、中村 忠博、北原 隆志、佐々木 均
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] 安全かつ効果的な眼疾患用新規遺伝子ベクターの開発 (2012)
  • Author(s): 佐々木均、兒玉幸修、黑﨑友亮、樋口則英、北原隆志、中村忠博
  • Organizer: 第32回日本眼薬理学会学術集会
  • Place of Presentation: ピアザ淡海（滋賀県大津市）
• [Presentation] Polyplex of pDNA with poly-L-lysine, poly-L-histidine, and γ-polyglutamic acid for biocompatible gene delivery system (2011)
  • Author(s): Yukinobu Kodama, Tomoaki Kurosaki, Kanoko Egashira, Tadahiro Nakamura, Takashi Kitahara, Hitoshi Sasaki
  • Organizer: 日本薬物動態学会第26回年会
  • Place of Presentation: 広島
  • Year and Date: 2011-11-17