Development of a new gene therapy with humanized mouse model : Autologous B cell regeneration with gene repair

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390285
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyushu University
• Principal Investigator: HARA Toshiro Kyushu University, 大学院・医学研究院, 教授 (40150445)
• Co-Investigator(Kenkyū-buntansha): KUSUHARA Kouichi 九州大学, 医学研究院, 准教授 (20243941) ; TAKADA Hidetoshi 九州大学, 大学病院, 准教授 (70294931) ; IHARA Kenji 九州大学, 大学病院, 講師 (80294932) ; NAKATSU Yoshimichi 九州大学, 医学研究院, 准教授 (00207820)
• Project Period (FY): 2007 – 2009
• Keywords: 遺伝子治療 / 原発性免疫不全症候群 / 伴性劣性無ガンマグロブリン血症 / アデノAAVハイブリッドベクター / NOD / SCID / γc完全欠失マウス / B細胞分化障害

Research Abstract

We have made a HD-Ad.AAV.BTK vector containing BTK exon6～exon19, TIMM8A and GFP-Hyg. After treatment of a male pre-B ALL cell line, Nalm6, with the vector, Hyg-resistant clones were obtained. Recombination of BTK gene was demonstrated in the clones by Southern blotting. In addition, vector genome was integrated to CD34-positive cells from male cord blood.

Research Products

• [Journal Article] T Cell Leukemia/Lymphoma 1 and Galectin-1 Regulate Survival/Cell Death Pathways in Human Naive and IgM+ Memory B Cells through Altering Balances in Bcl-2 Family Proteins (2009)
  • Author(s): Tabrizi SJ, Niiro H, Masui M, Yoshimoto G, Iino T, Kikushige Y, Wakasaki T, Baba E, Shimoda S, Miyamoto T, Hara T, Akashi K
  • Journal Title: J Immunol Pages: 1490-1499
• [Journal Article] Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in 75kDa anti-BTK anti-b-Actin WT 1 9 15 23 34 44 46 50kDa 37kDa 1kb+ 1 9 15 23 34 44 46 WT A B 2000 bp 1650 bp hyper-IgE syndrome. (2009)
  • Author(s): Minegishi Y, Saito M, Nagasawa M, Takada H, Hara T, Tsuchiya S, Agematsu K, Yamada M, Kawamura N, Ariga T, Tsuge I, Karasuyama H
  • Journal Title: J Exp Med. 206 Pages: 1291-301
• [Journal Article] FBP17 Mediates a Common Molecular Step in the Formation of Podosomes and Phagocytic Cups in Macrophages. (2009)
  • Author(s): Tsuboi S, Takada H, Hara T, Mochizuki N, Funyu T, Saitoh H, Terayama Y, Yamaya K, Ohyama C, Nonoyama S, Ochs HD
  • Journal Title: J Biol Chem. 284 Pages: 8548-56
• [Presentation] BTK gene repair by homologous recombination using helper-dependent adenovirus/adeno-associated virus hybrid vector. (2009)
  • Author(s): Ishimura M, Doi T, Takada H, Ohga S, Hara T
  • Organizer: 第39回日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 20091202-20091204
• [Presentation] ヘルパー依存型アデノ・アデノ随伴ウイルスハイブリッドベクターを用いた相同組換えによるBTK遺伝子修復研究 (2009)
  • Author(s): 石村匡崇、落合正行、山本裕之、古和温子、土居岳彦、高田英俊、大賀正一、楠原浩一、中津可道、續輝久、相澤絵美、三谷幸之介、原寿郎
  • Organizer: 第51回日本小児血液学会・第25回日本小児がん学会
  • Place of Presentation: 東京
  • Year and Date: 20091127-20091130
• [Presentation] ヘルパー依存型アデノ・アデノ随伴ウイルスハイブリッドベクターを用いた相同組換えによるBTK遺伝子修復研究 (2009)
  • Author(s): 石村匡崇、落合正行、山元裕之、古和温子、土居岳彦、高田英俊、大賀正一、楠原浩一、中津可道、續輝久、相澤絵美、三谷幸之介、原寿郎
  • Organizer: 第37回日本臨床免疫学会
  • Place of Presentation: 東京
  • Year and Date: 20091113-20091115
• [Presentation] ヒト化マウスにおけるヒトB細胞解析と新規XLAマウスモデル確率への応用 (2009)
  • Author(s): 土居岳彦、高田英俊、金兼弘和、宮脇利男、原寿郎
  • Organizer: 第112回日本小児科学会
  • Place of Presentation: 奈良
  • Year and Date: 20090417-20090419
• [Presentation] Rapid diagnostic system of primary immunodeficiency diseases in Japan (2009)
  • Author(s): Hangzhou
  • Organizer: Hara T The 5th ASPR
  • Place of Presentation: China
  • Year and Date: 2009-05-22
• [Book] 免疫疾患 (2010)
  • Author(s): 寿郎
  • Publisher: 標準小児科学(印刷中)
• [Remarks] ホームページ等なし