2003 Fiscal Year Final Research Report Summary
Longterm gene therapy of xeroderma pigmentosum group A mice using HVJ-liposomes.
| Project/Area Number |
14370258
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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 |
Dermatology
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| Research Institution | Kobe University (2003)
Kyoto University (2002) |
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Principal Investigator |
NISHIGORI Chikako Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50198454)
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| Project Period (FY) |
2002 – 2003
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| Keywords | xeroderma pigmentosum / HVJ-liposomes / gene therapy / nucleotide excision repair / skin tumor / ultraviolet light |
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| Research Abstract |
Xeroderma pigmentosum (XP) is an autosomalrecessibely inheritated disorder in which nucleotide excision repair is deficient, thus the patients with XP cause skin cancer of sun-exposed area in high frequency. Among XP complementation groups, XP complementation group A (XPA) reveals the severest clinical phenotype with neurological abnormalities and XPA is the most common type among Japanese XPA patients. The aim of this project is to challenge the gene therapy of XPA model mice in vivo with treating human XPA gene in the form of HVJ-liposomes, since one of our research goal is to establish the gene therapy for XPA patients. Two plasmids containing human XPA gene, pCAGGS-XPA or pcHA-XPA, which contains hemagultinin gene as a tag, was transfected and the repair ability was measured by unscheduled DNA syntshesis at post 24 or 48 hr UVC irradiation. Both recovered the repair efficiency in XPA mice cells. In in vivo study HVJ (Hemagluutinating Virus of Japan)-liposomes was used for introducing the plasmid containing human XPA gene into mice skin. HVJ-liposomes-XPA was injected intradermaly 24 hr before 4 kJ/m^2 of UVB irradiation or topically painted 48 hr before UVB irradiation. Unscheduled DNA synthesis of epidermal nuclei in mice injected XPA-HVJ liposmes was higher than that of control liposomes. Next we irradiated the mice with 500 J/m^2 of UVB 1-2 times per week for 3 months with or without treating HVJ-XPA-liposmes 24 or 48 hr prior to UVB irradiation. Both pcHA-XPA and pCAGGS-XPA encapsulated in HVJ-liposmes reduced the size, the number of the UV-induced tumors and elongate the survival duration. However, both treatment did not completely inhibit the tumor formation. The histology of the tumor was squamous cell carcinoma. In conclusion, the treatment of HVJ-XPA liposomes has effect on reducing the UV-induced tumors in XPA model mice.
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