2002 Fiscal Year Final Research Report Summary
Feasibility of MARCO(Mitochondrial antisense RNA for cytochrome C Oxidase) for the treatment of leukerniaz
| Project/Area Number |
11470207
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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 | 一般 |
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| Research Field |
Hematology
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| Research Institution | Teikyo University School of Medicine (2000-2002)
The University of Tokyo (1999) |
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Principal Investigator |
SHIRATUJI Naoki Department of medicine, Associated Professor, 医学部, 助教授 (00206301)
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| Co-Investigator(Kenkyū-buntansha) |
GOTO Moritaka Univ. of Nagoya, Department of Medicine, Assistant Professor, 医学部, 助手
MATSUDA Satoru Univ. of Nagoya, Department of Medicine, Associate Professor, 医学部, 助教授 (50242110)
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| Project Period (FY) |
1999 – 2002
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| Keywords | mitochondria / antisense RNA / cytochrome C oxidase / gene therapy / Adenovirus / liposome |
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| Research Abstract |
The plasmid which expressed MARCO: mitochondrial antisense RNA for cytochrome C oxidase was constructed with CMV promoter, and was introduced into murine leukemia cell line MOPC (B cell), EL-4 (T cell), and WEHI-3B (myelomonocytic) with liposomal delivery. The efficiency of the introduction of MARCO to each cell line was approximately 10 %. Cell-death was observed significantly in a time dependent manner in in vitro system. In in vivo system there were also observed elongated survival for 4 weeks when MARCO was administered to the tumor-burden mice for 3 days intra peritoneally, and intra venously. When MARCO was administered to the tumor-burden mice for 14 days with liposomal delivery, there were observed 3 months' elongated survival compared with the mock-transfected mice. There were also observed dose-dependency on the amount of the administered MARCO. The adverse effects were observed leukocytopenia for a transient period ( after 12 to 24 hours after the administration), and no other effects were observed to main organs which was determined with pathological findings. Also, recombinant Adenovirus which expressed MARCO was constructed with cosmid shattle vector originated from Adenovirus. The efficiency of the introduction to MOPC, EL-4, and WEHI-3B cells was approximately 50%. However, in in vitro, and in vivo study, cell-death effects were less than that observed with liposomal administration of MARCO. These data indicated that gene therapy using MARCO is feasible against leukemias, especially with liposomal delively. On the next step, we intend to use RNAi for the gene therapy against leukemias.
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