Topical application of viral vectors for epidermal gene transfer

Abstract

Efficient gene transfer with extended gene expression is essential for successful treatment of skin diseases using gene therapy. Previously we evaluated a physical gene transfer method (gene gun delivery) for its ability to transfect the epidermis in vivo. In this study, we tested two viral vectors for their ability to transduce murine epidermis through topical application. Both an adenoviral vector and a herpes simplex virus (HSV) amplicon vector transduced murine epidermis with high efficiency after topical application. Differences in amount and duration of transgene expression were compared between these two vectors. Quantitative analysis of reporter lacZ gene expression showed that the viral vector-mediated gene transfers were superior to gene-gun delivery of plasmid DNA. Significant necrosis and cytotoxicity, however, were observed in the HSV-treated skin. In addition, we show that murine epidermis developed hyperkeratosis and acanthosis 4 d after an adenoviral vector containing a human TGF-alpha expression unit was applied topically. Finally we demonstrate the feasibility of transduction of fetal skin in utero by intraamniotic injection of an adenovirus vector.