2003 Fiscal Year Final Research Report Summary
Development of gene therapy for dystrophic epidemolysis bullosa with artificial adhension molecule
Project/Area Number |
14370257
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Dermatology
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Research Institution | Osaka University (2003) Hirosaki University (2002) |
Principal Investigator |
TAMAI Katsuto Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (20236730)
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Project Period (FY) |
2002 – 2003
|
Keywords | Epidemolysis bullosa / Type VII collagen / Fibronectin / Ultrasonic sound / Chemical pealing |
Research Abstract |
Because of type VII collagen gene (COL7A1) defect, immune tolerance for type VII collagen must be disrupted in the patients of dystrophic epidermolysis bullosa (EB). However, since many EB patients express abnormal type VII collagen truncated after NC-1 domain which function to bind to the basement membrane, we have constructed expression vector of the artificial molecule composed of NC-1 domain of type VII collagen and fibronectin collagen binding domain chimera (NC-1/FNCBD) to expect adhesive activity at cutaneous basement membrane region and immune tolerance of the chimera molecule. Transfection of the NC-1/FNCBD expression vector in HaCat keratinocytes provided efficient expression of the chimera molecule both in the cells and the culture medium. This artificial peptide may function to rescue severe blistering phenotype of the dystrophic EB patients. To introduce the NC-1/FNCBD expression vector to the living skin, novel technology must be developed to introduce high molecular weight molecule, such as plasmid DNA, to the skin, as barrier function of the skin is strong enough to prohibit penetration of the molecule bigger than 1 kDa in size. We applied chemical pealing and ultrasonic sound (US) energy to introduce plasmid DNA to the skin. 50% glycolic acid (GA) treatment for 10 minutes was enough to break horny layer barrier function, and application of US energy on the GA-treated skin enabled introduction of the NC-1/FNCBD expression vector to the skin soaked in the plasmid solution, resulting in the expression of the NC-1/FNCBD molecule at dermo-epidernal junction.
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Research Products
(15 results)