| Project/Area Number |
09557207
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Human genetics
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| Research Institution | Nippon Medical School |
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Principal Investigator |
SHIMADA Takashi Nippon Medical School, Professor, 医学部, 教授 (20125074)
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| Co-Investigator(Kenkyū-buntansha) |
MIGITA Makoto Nippon Medical School, Assistant Professor, 医学部, 講師 (50256963)
YAMAMOTO Masao Nippon Medical School, Professor, 医学部, 教授 (60089662)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1997: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | Gene Therapy / Viral vectors / Gaucher disease / Hematopoietic stem cells / Gaucher病 / レトロウィルスベクター / AAVベクター / Gancher病 / 骨髄ストローマ細胞 / フィブロネクチン |
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| Research Abstract |
Gaucher disease, an autosomal recessive lysosomal storage disorder caused by a deficiency of glucocerebrosidase (GC), is an important target for human somatic cell gene therapy. In order to achieve the efficient gene transfer strategy for Gaucher disease, we attempted to optimize the conditions for retroviral mediated gene transfer into hematopoietic stem cells. Approximately 50 % of hematopoietic progenitor cells could be transduced by retroviral vectors using various cytokines, stroma cells, and fibronectin. However, this efficiency is still inadequate for genetic correction of the real hematopoietic stem cells. A major limitation of retroviral vectors appears to be their inability to infect growth arrested cells. To overcome this intrinsic problem, a retroviral vector derived from human immune-deficiency virus (HIV) that is able to infect terminally differentiated cells has been newly developed. We demonstrated that HIV vectors were capable of efficient gene transfer into non-dividing or rarely dividing cells such as hematopoietic cells, neurological cells, and muscle cells. HIV based vectors should be useful for gene therapy of type I Gaucher disease targeting hematopoietic stem cells. We have also shown that bone marrow contains multipotential stem cells that differentiate into neurological cells. Autologous bone marrow cells may be useful as carriers for ex vivo gene therapy for neurological symptoms of type II Gaucher disease.
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