DEPTH-TARGETED EFFICIENT GENE DELIVERY AND EXPRESSION IN THE SKIN BY PULSED ELECTRIC-FIELDS - AN APPROACH TO GENE-THERAPY OF SKIN AGING ANDOTHER DISEASES

The ability to target genes to the various layers, cell types, and app endages of the skin could be used to correct skin disorders, including those of aging such as wrinkling, as well as utilize specific cell ty pes for production of molecules useful elsewhere in the body. However, the stratum corneum acts as a significant physical barrier to gene tr ansfer into the skin. In this report we describe the ability to target and express the lacZ reporter gene to various depths of the dermis re gion in hairless mice. Skin-depth targeting is achieved by varying pul sed electrical fields and subsequent pressure from caliper-type electr odes on topically applied naked lacZ gene constructs. With electric pu lses and extended pressure, the maximum depth of lacZ expression in th e dermis and transfected cells was achieved at 370 mu m and 457 cells/ mm(2), respectively. Gene expression was observed only in the hair fol licles in the case of the control. (C) 1996 Academic Press, Inc.