Helper-dependent adenovirusvector and modified lentiviral vector mediated delivery of dystrophin for gene therapy of muscular dystrophy

• Project/Area Number: 20591003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Kumamoto University
• Principal Investigator: UCHINO Makoto Kumamoto University, 大学院・生命科学研究部, 教授 (20117336)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 筋ジストロフィー / 遺伝子治療 / ヘルパー依存アデノウイルス / 改変レンチウイルス / full-length dystrophin / dko mouse / whole-body plethysmography / helper-dependent adenovirus vector / lentivirus / lentivirus vector

Research Abstract

We showed that a highly efficient dystrophin-transduction to the mex and dko's diaphragm-achieved by simple intraperitoneal injection of a helper-dependent adenovirus vector (HDAdv) containing the full-length dystrophin expression cassette - provided beneficial results. we carried out the packaging of the full-length dystrophin cDNA in a genetically modified lentivirus with a useful, sufficiently functional titer that was successfully transduced into myogenic cells derived from the transgenic mdx mouse.

Research Products

• [Journal Article] Muscle fiber type-predominant promoter activity in lentiviral-mediated transgenic mouse. (2011)
  • Author(s): Suga T, Kimura E, Morioka Y, Ikawa M, Li S, Uchino K, Uchida Y, Maeda Y, Chamberlain JS, Uchino M.
  • Journal Title: PloS One in press
  • NAID: 120006957404
  • Peer Reviewed
• [Journal Article] Rescue from respiratory dysfunction bytransduction of full-length dystrophin to diaphragm via the peritoneal cavity in utrophin/dystrophin double knockout mice. (2011)
  • Author(s): Ishizaki M, Maeda Y, Kawano R, Suga T, Uchida Y, Uchida Y, Uchino K, Yamashita S, Kimura E, Uchino M.
  • Journal Title: Mol Ther In press
  • Peer Reviewed
• [Journal Article] Muscle fiber type-predominant promoter activity in lentiviral-mediated transgenic mouse (2011)
  • Author(s): Suga T, Kimura E, Morioka Y, Ikawa M, Li S, Uchino K, Uchida Y, Maeda Y, Chamberlain JS, Uchino M.
  • Journal Title: PloS ONE Volume: (In press)
  • NAID: 120006957404
  • Peer Reviewed
• [Journal Article] Rescue from respiratory dysfunction by transduction of full-length dystrophinto diaphragm via the peritoneal cavity in mouse with muscular dystrophy (2011)
  • Author(s): Ishizaki M, Maeda Y, Kawano R, Suga T, Uchida Y, Uchida Y, Uchino K, Yamashita S, Kimura E, Uchino M.
  • Journal Title: Mol Ther Volume: (In press)
  • Peer Reviewed
• [Journal Article] Packaging and delivery of full-length dystrophin in a lentiviral vector (2011)
  • Author(s): Uchino K, kimura E, SugaT, Koide T, Mori A, Uchida Y, Yamashita S, Maeda Y, et al.
  • Journal Title: PloS ONE Volume: (In press)
  • Peer Reviewed
• [Journal Article] Transduction of full-length dystrophin to multiple skeletal muscles improves motor performance and life span in utrophin/dystrophin double knockout mice (2008)
  • Author(s): Kawano R., et al.
  • Journal Title: Mol Ther 18 Pages: 825-831
  • Peer Reviewed
• [Journal Article] Mdx respiratory impairment following fibrosis of the diaphragm (2008)
  • Author(s): Ishizaki M., et al.
  • Journal Title: Neuromuscul disord 18 Pages: 342-348
  • Peer Reviewed
• [Presentation] Muscle fiber type-predominant promoter activity in lentiviral-mediated transgenic mouse (2010)
  • Author(s): Suga T, Uchino M, et al.
  • Organizer: 18^<th> Annual Congress of the European Society of Gene and Cell Therapy
  • Place of Presentation: Stella Polare convention center, Milano,イタリア
  • Year and Date: 2010-10-24
• [Presentation] Lentivirat vector mediated delivery of full-length dystrophin for gene therapy of muscular dystrophy (2010)
  • Author(s): Kimura E, Uchino M, et al.
  • Organizer: 15^<th> International Congress of the world muscle Society
  • Place of Presentation: Kumamoto City Hall, Kumamoto,日本
  • Year and Date: 2010-10-15
• [Presentation] Lentiviral vector mediated delivery of full-length dystrophin for gene therapy of muscular dystrophy (2010)
  • Author(s): Kimura E, Uchino M, et al.
  • Organizer: 13^<th> Annual Meeting of the American Society of Gene and Cell Therapy
  • Place of Presentation: Marriott Wardman Park Hotel Washington DC.アメリカ
  • Year and Date: 2010-05-20
• [Presentation] Lentiviral vector mediated delivery of full-length dystrophin for gene therapy of muscular dystrophy. (2010)
  • Author(s): Kimura E, Uchino K, Suga T, Ishizaki M, Koide T, Uchida Y, Maeda Y, Yamashita S, Chamberlain JS, Uchino M.
  • Organizer: 13^<th> Annual Meeting of the American Society of Gene and Cell Therapy
  • Place of Presentation: Marriott Wardman Park Hotel, Washington DC, USA.
• [Presentation] Transduction of full-length dystrophin to diaphragm ameliorates respiratory dysfunction in severe dystrophic mouse (2009)
  • Author(s): Ishizaki M., et al.
  • Organizer: The European Society of Gene and Cell Therapy
  • Place of Presentation: Convention Center at Hannover Faiground, Hannover, Germany
  • Year and Date: 2009-11-23
• [Presentation] Gene delivery to dystrophic diaphragm by the helper-dependent adenovirus vector(HDAdv)-mediated full-length dystrophin expression (2008)
  • Author(s): Ishizaki M., et al.
  • Organizer: American Society of Gene Therapy
  • Place of Presentation: Boston, USA
  • Year and Date: 2008-05-30
• [Presentation] シンポジウム2.新しい神経治療をめぐってーミオパチー領域における最新の治療戦略 (2008)
  • Author(s): 内野誠
  • Organizer: 第26回日本神経治療学会
  • Place of Presentation: 新横浜プリンスホテル
• [Book] 最新神経病学(分担:筋肉疾患) (2008)
  • Author(s): 内野誠
  • Total Pages: 66
  • Publisher: 金芳堂
• [Remarks] ホームページ等
  • URL: http://www.kumamoto-neuro.jp/index.html