Gene transduction in skin cells: preventing cancer in xeroderma pigmentosum mice.
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 gene was 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.
Marchetto
Maria Carolina N
MC
Department of Microbiology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo 05508-900, SP, Brazil.
Muotri
Alysson R
AR
Burns
Dennis K
DK
Friedberg
Errol C
EC
Menck
Carlos F M
CF
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012867:Skin / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D014161:Transduction, Genetic; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D051760:Xeroderma Pigmentosum Group A Protein
D004268:DNA-Binding Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse