Gene transduction in skin cells: Preventing cancer in xeroderma pigmentosum mice

被引:36
|
作者
Marchetto, MCN
Muotri, AR
Burns, DK
Friedberg, EC
Menck, CFM [1 ]
机构
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508900 Sao Paulo, SP, Brazil
[2] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA
[3] Univ Texas, SW Med Ctr, Dept Pathol, Lab Mol Pathol, Dallas, TX 75235 USA
关键词
DNA repair; gene therapy; ultraviolet; keratinocytes;
D O I
10.1073/pnas.0406304101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
UV radiation is the most common risk factor for skin cancer. Patients with the autosomal recessive DNA repair disorder xeroderma pigmentosum (XP) suffer high incidence of skin cancer after sunlight exposure. XP-mutant mice are attractive models to study this syndrome, as they, too, develop UV radiation-induced skin tumors, mimicking the human phenotype. Recombinant adenovirus carrying the human XPA genewas used for in vivo gene therapy in UVB-irradiated skin of such mice. Virus s.c. injection led to the expression of the XPA protein in basal keratinocytes and prevented deleterious effects in the skin, including late development of squamous cell carcinoma. Thus, efficient adenovirus gene delivery to the skin is a promising tool for reconstitution of specific DNA repair defects in XP patients.
引用
收藏
页码:17759 / 17764
页数:6
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