Preclinical Hemophilia Gene Therapy Study with Non-human Primates
| Project/Area Number |
20591155
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Jichi Medical University |
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Principal Investigator |
MIMURO Jun Jichi Medical University, 医学部, 准教授 (10221607)
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| Co-Investigator(Kenkyū-buntansha) |
MADOIWA Seiji 自治医科大学, 医学部, 講師 (70296119)
OHMORI Tsukasa 自治医科大学, 医学部, 講師 (70382843)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 血友病 / 遺伝子治療 / 細胞移植 / 第VIII因子 / 第IX因子 / 第IX |
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| Research Abstract |
The Hemophilia gene therapy study was carried out according to the research plan. We have completed the FIX gene expression study with adeno-associated virus (AAV) vectors in mice for hemophilia B gene therapy and the hemophilia B gene therapy preclinical study is currently conducted with macaques. The AAV8 vector carrying the macaque FIX T262A was effective to express macaque FIX T262A to the therapeutic level in anti-AAV8 antibody-negative macaques whereas the vector was unable to express macaque FIX T262A to the therapeutic level in anti-AAV8 antibody-positive macaques. The novel vector-injection method for evading the inhibitory effect of anti-AAV8 antibody was developed and was effective to express the transgene-derived macaque FIX T262A in anti-AAV8 antibody-positive macaques. Human FVIII could be expressed with the AAV8 vector to the therapeutic level in FVIII deficient mice. A novel hemophilia A model animal (cloned hemophilia A pig) was generated by nuclear transfer cloning. The efficient and site specific integration of FVIII gene into the chromosome 19 was achieved with the AAV2 Rep gene. New monoclonal antibodies raised against B domain-deleted human FVIII were developed and used to quantify B domain deleted human FVIII specifically.
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Report
(4 results)
Research Products
(94 results)
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[Journal Article] Vinculin is indispensable for repopulation by hematopoietic stem cells, independent of integrin function.2010
Author(s)
Ohmori, T., Kashiwakura,Y., Ishiwata, A., Madoiwa,S., Mimuro,J., Furukawa, Y., Sakata, Y.
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Journal Title
J Biol Chem 285(41)
Pages: 31763-31773
Related Report
Peer Reviewed
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[Journal Article] Mutant macaque factor IX T262A:A tool for hemophilia B gene therapy studies in macaques.2010
Author(s)
Ishiwata A., Mimuro J., Mizukami H., Kashiwakura Y., Yasumoto A., Sakata A., Ohmori T., Madoiwa S., Ono F., Shima M., Yoshioka A., Ozawa K., Sakata Y.
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Journal Title
Thromb Res 125(6)
Pages: 533-537
Related Report
Peer Reviewed
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[Journal Article] Impacto of acute cellular rejection on coagulation and f ibrinolysis biomarkers within the immediate post-operative reriod in pediatric liver transplantation.2010
Author(s)
Mimuro J., Mizuta K., Kawano Y., Hishikawa S., Hamano A., Kashiwakura Y., Ishiwata A., Ohmori T., Madoiwa S., Kawarasaki H., Sakata Y.
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Journal Title
Pediatr Transplant 14(3)
Pages: 369-376
Related Report
Peer Reviewed
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[Journal Article] Induction of factor VIII-specific unresponsiveness by intrathymic factor VIII injection in murine hemophilia A.2009
Author(s)
Madoiwa S., Yamauchi T., Kobayashi E., Hakamata Y., Dokai M., Makino N., Kashiwakura Y., Ishiwata A., Ohmori T., Mimuro J., Sakata Y.
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Journal Title
J Thromb Haemost 7(5)
Pages: 811-824
Related Report
Peer Reviewed
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[Journal Article] Antagonism of sphingosine 1-phosphate receptor-2 enhances migration of neural progenitor cells toward an area of brain infarction.2008
Author(s)
Kimura.,A., Ohmori,T., Kashiwakura.Y., Ohkawa,R., Madoiwa,S., Mimuro,J., Shimazaki,K., Hoshino,Y., Yatomi,Y., Sakata,Y.
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Journal Title
Stroke. Dec 39(12)
Pages: 3411-7
Related Report
Peer Reviewed
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[Journal Article] Phenotypic orrection of hemophilia A by ectopic expression of activated factor FVII in platelets.2008
Author(s)
Ohmori,T., Ishiwata,A., Kashiwakura,Y., Madoiwa, S., Mitomo,K., Suzuki,H., Hasegawa,M., Mimuro,J.,Sakata,Y.
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Journal Title
Mol Ther 16(8)
Pages: 1359-1363
Related Report
Peer Reviewed
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[Journal Article] Determinants of thrombbbbf thrombthrombof thrombthrombf thromb thrombrombrombhrombeneration, fibrinolytic activity, and endothelial dysfunction in dual-antiplatelet therapy : nvolvement of factors other than platelet aggregability in Virchow's triad.2008
Author(s)
Yano Y., Ohmori T., Hoshide S., Madoiwa S., Yamamoto K., Katsuki T., Mitsuhashi T., Mimuro J., Shimada K., Kario K., Sakata Y.
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Journal Title
European Heart Journal Jul 29(14)
Pages: 1729-1738
Related Report
Peer Reviewed
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[Presentation] Choice of small-sized promother for AAV-medlated factor IX expression in skeletal muscle.2010
Author(s)
Akihiro Kume, Hiroya Yagi, Hiroaki Mizukami, Masashi Urabe, Tomonori Tsukahara, Akira Ishiwata, Jun Mimuro, Seiji Madoiwa, Tsukasa Ohmori, Yoichi Sakata, Keiya Ozawa
Organizer
第16回日本遺伝子治療学会学術集会
Place of Presentation
宇都宮
Related Report
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[Presentation] エンドトキシン症における血栓性微小血管障害の発症機序の解析2008
Author(s)
柏倉裕志, 三室淳, 新村真則, 小野智子, 石渡彰, 土海桃子, 大森司, 窓岩清治, 岡田清孝, 松尾理, 坂田洋一
Organizer
第70回日本血液学会総会
Place of Presentation
京都
Related Report
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[Presentation] 非ヒト霊長類モデルにおける血友病B 遺伝子治療の基礎的検討2008
Author(s)
石渡彰, 三室淳, 水上浩明, 小野文子,柏倉裕志, 大森司, 諏合輝子, 窓岩清治, 保富康宏, 小澤敬也, 坂田洋一
Organizer
第70回日本血液学会総会
Place of Presentation
京都
Related Report
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