Development of gene therapy against vascular diseases using polymeric micellar gene vector with versatile functions

2010 Fiscal Year Self-evaluation Report

• Project/Area Number: 20689024
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Nagasaki University (2010-2011); The University of Tokyo (2008-2009)
• Principal Investigator: OBA Makoto The University of Tokyo, 医歯薬学総合研究科, 准教授 (20396716)
• Project Period (FY): 2008 – 2011
• Keywords: 血管外科学 / 遺伝子治療 / ドラッグデリバリーシステム

Research Abstract

本研究では、全身投与で患部の標的化が可能な遺伝子ベクターの開発を目的とする。ベクターを投与してから効果を発揮するまでの各過程、すなわち、血液中における安定性、血管疾患部位への特異的な取り込み、細胞内に取り込まれた後の核に到達するまでの細胞内動態、ミセルに内包しているプラスミドの放出に関して、in vitroおよびin vivoで詳細に検討を行い、各機能の最適条件を探る。最終的には最適条件の各機能を兼ね備えた高分子ミセルを作製して評価を行うとともに、治療遺伝子を搭載したミセルを用い血管疾患モデルに対する治療の評価を行う。

Research Products

• [Journal Article] Enhanced transfection with silica-coated polyplexes loading plasmid DNA (2010)
  • Author(s): Kanjiro Miyata, Noha Gouda, Hiroyasu Takemoto, Makoto Oba, Yan Lee, Hiroyuki Koyama, Yuichi Yamasaki, Keiji Itaka, Nobuhiro Nishiyama, Kazunori Kataoka
  • Journal Title: Biomaterials 31(17) Pages: 4764-4770
  • Peer Reviewed
• [Journal Article] Antiangiogenic gene therapy of solid tumor by systemic injection of polyplex micelles loading plasmid DNA encoding soluble Flt-1 (2010)
  • Author(s): Makoto Oba, Yelena Vachutinsky, Kanjiro Miyata, Mitsunobu R.Kano, Sorato Ikeda, Nobuhiro Nishiyama, Keiji Itaka, Kohei Miyazono, Hiroyuki Koyama, Kazunori Kataoka
  • Journal Title: Mol.Pharmaceutics 7(2) Pages: 501-509
  • Peer Reviewed
• [Journal Article] Enhanced percolation and gene expression in tumor hypoxia by PEGylated polyplex micelles (2009)
  • Author(s): Muri Han, Makoto Oba, Nobuhiro Nishiyama, Mitsunobu R.Kano, Shinae Kizaka-Kondoh, Kazunori Kataoka
  • Journal Title: Mol.Ther 17(8) Pages: 1404-1410
  • Peer Reviewed
• [Journal Article] Polyplex micelles with cyclic RGD peptide ligands and disulfide crosslinks directing to the enhanced transfetion via controlled intracellular trafficking (2008)
  • Author(s): Makoto Oba, Kazuhiro Aoyagai, Kanjiro Miyata, Yu Matsumoto, Keiji Itaka, Nobuhiro Nishiyama, Yuichi Yamasaki, Hiroyuki Koyama, Kazunori Kataoka
  • Journal Title: Mol.Pharmaceutics 5(6) Pages: 1080-1092
  • Peer Reviewed
• [Journal Article] Polyplexes from poly(aspartamide) bearing 1, 2-diaminoethane side chains induce pH-selective, endosomal membrane destabilization with amplified transfection and negligible cytotoxicity (2008)
  • Author(s): Kanjiro Miyata, Makoto Oba, Masataka Nakanishi, Shigeto Fukushima, Yuichi Yamasaki, Hiroyuki Koyama, Nobuhiro Nishiyama, Kazunori Kataoka
  • Journal Title: J.Am.Chem.Soc 130(48) Pages: 16287-16294
  • Peer Reviewed
• [Presentation] Antiangiogenic gene therapy of subcutaneous pancreatic tumor by systemic injection of polyplex micelles loading sFlt-1 plasmid DNA (2010)
  • Author(s): Makoto Oba, Yelena Vachutinsky, Kanjiro Miyata, Nobuhiro Nishiyama, Hiroyuki Koyama, Kazunori Kataoka
  • Organizer: PACIFICHEM 2010
  • Place of Presentation: Honolulu
  • Year and Date: 20101215-20101220
• [Presentation] 化学量論的な電荷比を超えて会合する高分子ミセル型遺伝子ベクターの設計とその機能評価 (2010)
  • Author(s): 大庭誠, 宮田完二郎, 長田健介, 福島重人, 西山伸宏, 小山博之, 片岡一則
  • Organizer: 遺伝子・デリバリー研究会第10回シンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 20100602-03
• [Presentation] Anti-angiogenic gene therapy of pancreatic adenocarcinoma using ppolyplex micelles with plasmid DNA encoding soluble form of Flt-1 (2009)
  • Author(s): Makoto Oba, Yelena Vachutinsky, Kanjiro Miyata, Sorato Ikeda, Nobuhiro Nishiyama, Hiroyuki Koyama, Kazunori Kataoka
  • Organizer: The 10th US-Japan Symposium on Drug Delivery System
  • Place of Presentation: Maui
  • Year and Date: 20091216-20091220
• [Presentation] 高分子ミセル型遺伝子ベクターを用いた膵臓がんの遺伝子治療法の開発 (2009)
  • Author(s): 大庭誠, Vachutinsky Yelena, 宮田完二郎, 狩野光伸, 宮園浩平, 西山伸宏, 小山博之, 片岡一則
  • Organizer: 第31回日本バイオマテリアル学会
  • Place of Presentation: 京都
  • Year and Date: 20091116-20091117
• [Presentation] Functional assessment of polyplex micelles with cyclic RGD peptide ligands and disulfide crosslinked core (2008)
  • Author(s): Makoto Oba, Kazuhiro Aoyagai, Kanjiro Miyata, Nobuhiro Nishiyama, Hiroyuki Koyama, Kazunori Kataoka
  • Organizer: 35th Annual Meeting & Exposition of the Controlled Release Society
  • Place of Presentation: New York
  • Year and Date: 20080712-20080716
• [Patent(Industrial Property Rights)] 電荷変換型三元系ポリプレックス (2009)
  • Inventor(s): 片岡一則, 宮田完二郎, Lee Yan, 大庭誠, 西山伸宏, 比木茂寛, 三條 舞, Kim Hyn Jin
  • Industrial Property Rights Holder: 片岡一則, 宮田完二郎, Lee Yan, 大庭誠, 西山伸宏, 比木茂寛, 三條 舞, Kim Hyn Jin
  • Industrial Property Number: 特許.WO2009-133968
  • Filing Date: 2009-04-30