In vivo transduction of mouse epidermis with recombinant retroviral vectors: implications for cutaneous gene therapy.
Gene-based therapies may provide a way to treat inherited skin disorders but current approaches suffer serious limitations. The surgical procedures required to transplant ex vivo modified keratinocytes are likely to result in scarring and contracture, thereby limiting the area that can be treated. In addition, none of the methods currently available for in vivo gene transfer to epidermis leads to long-term transgene expression. The goal of this study was to develop a means for in vivo gene transfer to epidermis that would result in long-term transgene expression. We report here the first successful in vivo gene transfer that results in sustained transgene expression in epidermis. Hyperplastic mouse skin was transduced by direct injection of VSV-G pseudotyped retroviral vectors encoding the LacZ reporter gene. In mice tolerant to beta-galactosidase (beta-gal), transgene expression was noted in hair follicles and interfollicular epidermis for the duration of the experiment (16 weeks after transduction). Based on the kinetics of epidermal turnover in mouse skin, expression for this length of time strongly suggests stem cell transduction. In immunocompetent mice intolerant to beta-gal, transgene expression was lost by 3 weeks after transduction, concurrent with the onset of host immune responses to the transgene product.
Ghazizadeh
S
S
Department of Oral Biology and Pathology, SUNY at Stony Brook, NY 11794-8702, USA.
Harrington
R
R
Taichman
L
L
D000818:Animals; D004817:Epidermis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D018859:Hair Follicle / Q000201:enzymology; D006965:Hyperplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D018632:Mice, Inbred SENCAR; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D012190:Retroviridae / Q000235:genetics*; D019076:Transgenes; D001616:beta-Galactosidase / Q000235:genetics
D001616:beta-Galactosidase