| Project/Area Number |
15590844
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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 |
Kidney internal medicine
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| Research Institution | Niigata University |
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Principal Investigator |
MARUYAMA Hiroki Niigata University, Medical and Dental Hospital, Assistant, 医歯学総合病院, 助手 (10293218)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | naked DNA / CAG promoter / Fabry disease / α-galactosidase / hydrodynamic-based transfection / kidney-targeted gene transfer / renal vein / catheter / α-galactosidase A / hydrodynamics-based transfection / kidny-targeted gene transfer |
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| Research Abstract |
We recently developed a novel kidney-targeted gene transfer technique, using the retrograde renal vein injection of naked plasmid DNA and indicated that the kidney serves as a depot organ for the production of therapeutic proteins. Fabry disease is an X-linked recessive inborn metabolic disorder characterized by systemic and vascular accumulation of globotriaosylceramide (Gb3) caused by a deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A). Gene therapy is expected to revolutionize the treatment of Fabry disease. We examined the α-Gal A transfer to the treatment of mice with α-Gal A knock out (Fabry mice). Naked plasmid DNA expressing human α-Gal A (pKSCX-α-Gal A) solution was rapidly injected into the left kidneys via the retrograde renal vein. pKSCX solution was similarly injected into control mice (pKSCX mice).
We confirmed the presence of vector-derived α-Gal A mRNA in the left kidneys by reverse transcriptase polymerase chain reaction and observed plasma α-Gal A levels in pKSCX-α-Gal A-injected mice. Compared with the pKSCX mice, the pKSCX-α-Gal A mice showed significant therapeutic effects: increase of α-Gal A in injected kidney, liver, heart, and decrease of Gb3 in heart, bilateral kidneys, liver, spleen confirmed by thin-layer chromatography analysis.
These results demonstrate that kidney-targeted pKSCX-α-Gal A gene transfer by retrograde renal vein injection reduces systemic accumulation of Gb3 in Fabry mice.
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