Open AccessGene transduction in skin cells: Preventing cancer in xeroderma pigmentosum mice
Author(s) -
Maria C. Marchetto,
Alysson R. Muotri,
Dennis K. Burns,
Errol C. Friedberg,
Carlos Frederico Martins Menck
Publication year - 2004
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0406304101
Subject(s) - xeroderma pigmentosum , skin cancer , cancer research , biology , dna repair , genetic enhancement , human skin , mutant , photodermatosis , transduction (biophysics) , gene , basal cell carcinoma , dna damage , nucleotide excision repair , cancer , dna , microbiology and biotechnology , genetics , medicine , pathology , basal cell , biochemistry
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.