Homologous recombination-mediated gene correction for Adenosine deaminase deficiency

• Project/Area Number: 23791147
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: UCHIYAMA Toru 東北大学, 病院, 助教 (10436107)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 原発性免疫不全症 / 遺伝子治療 / 相同組換え / iPS細胞 / 造血幹細胞 / 相同組み替え / ADA欠損症

Research Abstract

iPS cells were derived from skin fibroblasts of ADA deficiency patients. While AAV-mediated gene targeting for the homologous recombination, followed by the selection with deoxyadenosine, was performed, corrected clones were not obtained. iPS cells showed the differentiation into T and B lymphocytes in the culture with OP9 stromal cells. This system is thought to be useful for the functional analysis of corrected ADA gene in iPS cells.

Research Products

• [Journal Article] Interstitial lung disease in two brothers with novel compound heterozygous ABCA3 mutations. (2013)
  • Author(s): Kitazawa H, Moriya K, Niizuma H, Kawano K, Saito-Nanjo Y, Uchiyama T, Rikiishi T, Sasahara Y, Sakamoto O, Setoguchi Y, Kure S
  • Journal Title: European Journal of Pediatrics Volume: 172(7) Pages: 953-7
  • DOI: 10.1007/s00431-013-1977-8
  • Peer Reviewed
• [Journal Article] Development of a Multi-Step Leukemogenesis Model of MLL-Rearranged Leukemia Using Humanized Mice (2012)
  • Author(s): Moriya K, Suzuki M, Watanabe Y, Takahashi T, Aoki Y, Uchiyama T, Kumaki S, Sasahara Y, Minegishi M, Kure S, Tsuchiya S, Sugamuta K, Ishii N.
  • Journal Title: PLos One Volume: 7(6)
  • Peer Reviewed
• [Journal Article] Foamy virus vector-mediated gene correction of a mouse model of Wiskott-Aldrich syndrome. (2012)
  • Author(s): Uchiyama T, Adriani M, Jagadeesh GJ, Paine A, Candotti F
  • Journal Title: Mol.Ther Volume: 20(6) Pages: 1270-1279
  • DOI: 10.1038/mt.2011.282
  • Peer Reviewed
• [Journal Article] Successful cord blood transplantation with reduced-intensity conditioning for childhood cerebral X-linked adrenoleukodystrophy at advanced and early stages. (2012)
  • Author(s): Niizuma H, Uematsu M, Sakamoto O, Uchiyama T, Horino S, Onuma M, Matsuhashi T, Rikiishi T, Sasahara Y, Minegishi M, Tsuchiya S.
  • Journal Title: Pediatr Transplant. Volume: 16(2)
  • DOI: 10.1111/j.1399-3046.2011.01539.x
  • Peer Reviewed
• [Journal Article] Development of a multi-step leukemogenesis model of MLL-rearranged leukemia using humanized mice. (2012)
  • Author(s): Moriya K, Suzuki M, Watanabe Y, Takahashi T, Aoki Y, Uchiyama T, Kumaki S, Sasahara Y, Minegishi M, Kure S, Tsuchiya S, Sugamura K, and Ishii N.
  • Journal Title: PLoS One Volume: 7(6)
  • DOI: 10.1371/journal.pone.0037892
  • Peer Reviewed
• [Journal Article] Defective inhibition of B-cell proliferation by Wiskott-Aldrich syndrome protein-deficient regulatory T cells (2011)
  • Author(s): Adriani M, Jones KA, Uchiyama T, Kirby MR, Silvin C, Anderson SM, Candotti F
  • Journal Title: Blood Volume: 117(24) Pages: 6608-11
  • DOI: 10.1182/blood-2010-12-322834
  • Peer Reviewed
• [Journal Article] Interstitial lung disease in two brothers with novel compound heterozygous ABCA3 mutations
  • Author(s): Kitazawa H., Moriya K., Niizuma H., Kawano K., Saito-Nanjo Y., Uchiyama T., Rikiishi T., Sasahara Y., Sakamoto O., Setoguchi Y., Kure S
  • Journal Title: Eur J Pediatr Volume: (In press)
  • Peer Reviewed
• [Journal Article] Successful cord blood transplantation with reduced-intensity conditioning for childhood cerebral X-linked adrenoleukodystorophy at advanced and early stages
  • Author(s): Niizuma H, Uematsu M, Sakamoto O, Uchiyama T, Horino S, Onuma M, Matsuhashi T, Rikiishi T, Sasahara Y, Minegishi M, Tsuchiya S.
  • Journal Title: Pediatr. Transplant Volume: 16(2)
  • Peer Reviewed
• [Presentation] Development of Foamy Virus Vector System for Primaryimmunodeficiencies (2012)
  • Author(s): Toru Uchiyama 、Satoshi Horino 、Yoji Sasahara、Naoto Ishii、Fabio Candotti
  • Organizer: 第18回日本遺伝子治療学会
  • Place of Presentation: 熊本
  • Year and Date: 2012-06-28
• [Presentation] Spontaneous reversionを伴う原発性免疫不全症2症例における長期的臨床経過の検討 (2012)
  • Author(s): 笹原洋二、佐藤美季、斉藤由佳、小沼正栄、入江正寛、内山徹、力石健、呉繁夫
  • Organizer: 第115回日本小児科学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2012-04-20
• [Presentation] 骨髄非破壊的前処置にて同種骨髄移植を施行した慢性活動性EBV感染症4例の臨床的検討 (2012)
  • Author(s): 笹原洋二、渡辺祐子、小沼正栄、新妻秀剛、内山徹、力石健、峯岸政好、久間木悟、土屋滋
  • Organizer: 第34回日本造血幹細胞移植学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2012-02-24
• [Presentation] RISTを施行した当科年長児および成人期WAS/XLT3症例の臨床的検討 (2012)
  • Author(s): 笹原洋二、力石健、北沢博、内山徹、森尾友宏、峯岸政好、久間木悟、土屋滋
  • Organizer: 第5回日本免疫不全症研究会
  • Place of Presentation: 東京
  • Year and Date: 2012-01-21
• [Presentation] リツキシマブが有効であった乳児自己免疫性溶血性貧血の1例 (2012)
  • Author(s): 森谷邦彦、松橋徹朗、小沼正栄、内山徹、力石健、浅田洋司、鈴木潤、笹原洋二、呉繁夫
  • Organizer: 第54回小児血液・がん学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Development of Foamy virus vectors for primary immunodeficiencies. (2012)
  • Author(s): 内山徹
  • Organizer: 第18回日本遺伝子治療学会
  • Place of Presentation: 熊本
• [Presentation] Spontaneous reversionを伴う原発性免疫不全症２症例における長期的臨床経過の検討 (2012)
  • Author(s): 笹原洋二
  • Organizer: 第115回日本小児科学会学術集会
  • Place of Presentation: 福岡
• [Presentation] リツキシマブが有効であった乳児自己免疫性溶血性貧血の一例 (2012)
  • Author(s): 森谷邦彦
  • Organizer: 第54回小児血液がん学会
  • Place of Presentation: 横浜
• [Presentation] SKY法が複雑型染色体異常の同定に有用であった急性白血病の2例 (2011)
  • Author(s): 片山紗乙莉、小沼正栄、内山徹、新妻秀剛、力石健、笹原洋二、呉繁夫
  • Organizer: 第53回日本小児血液・がん学会学術集会
  • Place of Presentation: 前橋
  • Year and Date: 2011-11-25
• [Presentation] フォーミーウイルスベクターによるWiskott-Aldrich症候群への遺伝子治療 (2011)
  • Author(s): 内山徹、Fabio Candotti、土屋滋
  • Organizer: 第114回日本小児科学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-08-12
• [Presentation] The progress of stem cell gene therapy for primary immunodefici- ency (2011)
  • Author(s): Toru Uchiyama
  • Organizer: 第17回日本遺伝子治療学会学術集会、シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2011-07-15