Development of new gene therapy for metabolic disorder of the liver -in vivo gene transfection using Particle Delivery System-
| Project/Area Number |
07671323
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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 |
General surgery
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| Research Institution | Jichi Medical School |
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Principal Investigator |
KOBAYASHI Eiji Jichi Medical School, Department of clinical Pharmacology, Associate Professor, 医学部, 助教授 (00245044)
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| Co-Investigator(Kenkyū-buntansha) |
KAGAWA Yasuo Jichi Medical School, Department of Biochemistry I., Professor, 医学部, 教授 (30048962)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | gene therapy / gene gun / metabolic disorder / cancer therapy / 肝酵素欠損病 |
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| Research Abstract |
We studied the in vivo gene transfection using gene gun, formerly called particle delivery system for congenially hepatic disorder disease. To develop this method, we tested 4 kinds of gene guns (Geneblaster 1221, Idera Gie-III,Hammer type, and Hand-held type) in culture cells and liver of living rats. Gold particles coated with CMV beta-galactosidase were bombarded into ex vivo and in vivo. The galactosidase activity was estimated in both systems. Au particles coated with CMV A-18 (UDP-glucuronosy transferase) were also done several times into the liver of Gunn rats which have a mutant lacking bilirubin UDP-glucuronosy transferase.
The best result was obtained by using a newly developed hand-held gene delivery system. The beta-galactosidose gene introduced into the rat liver with the An particle by He gas pressure of 250 psi, was expressed (1.2 mu units/mu g protein) in a limited area of the liver surface (8*8mm, depth 2mm). However, the serum level of bilirubine was not returned to that of the normal rats. Ex vivo gene transfection to the stem cells has been considered to be satiable for systemic metabolic disorder, but the in situ intracellular delivery with gene gun was fast, simple and versatile. A new effective method might be developed for solid cancer by mixing several kinds of DNA.
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Report
(3 results)
Research Products
(11 results)
