| Project/Area Number |
11670206
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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 |
Experimental pathology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KITAGAWA Masanobu TokyoMedical and Dental University, Department of Pathology and Immunology, Associate Professor, 大学院・医歯学総合研究科, 助教授 (10177834)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | retrovirus / Friend leukemia virus / gene therapy / レトロウィルス / フレンド白血病ウィルス / Fv-4 |
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| Research Abstract |
To establish the gene therapy model for retrovirus-induced disease, experiments using murine Friend leukemia virus (FLV) system were performed. We transduced the Fv-4^r gene that was the host resistant gene against ecotropic murine leukemia virus found in wild mouse. This gene encodes a truncated form of ENV protein which would bind to the receptor of the virus to block viral infection of the same receptor-specificity.
First of all, we searched for the condition to produce gene transfer system with good expression efficacy. Transduced Fv-4^r gene was well expressed in the hematopoietic cells and thus we could generate the bone marrow chimera mice by transplantation of Fv-4^r transduced bone marrow cells. Mice transduced with Fv-4^r gene were resistant to FLV-infection.
Next, mechanisms for the resistance by transduced Fv-4^r gene in bone marrow chimera mice were examined. By using FLV-ENV-GFP system, we clarified the receptor interference effect of Fv-4^r gene product in bone marrow chimera mice.
Finally, we analyzed the Fv-4^r gene therapy effect in immunosuppressed hosts. Fv-4^r gene therapy was also effective in thymectomized mice.
In summary, our gene therapy model was effective for resisting FLV-induced disease and the efficacy was transferred through receptor interference mechanism by the gene product. Because the therapy was effective even under the immunosuppressed condition of the hosts, human diseases by retrovirus such as AIDS would also be the target of this kind of gene therapy.
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