Enhanced cutaneous gene delivery following intradermal injection of naked DNA in a high ionic strength solution

Intradermal injection of naked DNA results in gene transfer to skin cells, but the efficiency of this gene transfer method is relatively low and variable. We have systematically optimized several parameters to obtain reproducible, high-level gene transfer to the mouse skin. Older mice (approximately 7 weeks) showed a significant decrease in gene expression compared with younger mice (4-5 weeks old). The composition of the solvent vehicle (electrolyte versus nonelectrolyte) strongly affected gene expression in the skin. A higher level of gene expression was achieved when naked DNA was dissolved in isotonic phosphate buffered saline solution compared with isotonic dextrose solution. Finally, transfection efficiency in older mice was greatly improved by increasing the ionic strength of the solvent vehicle. The improved transfection efficiency was due to an enhanced DNA uptake by the skin cells. Gene transfer was most evident in the subdermal smooth muscle cells and epidermal cells. With the optimized conditions, gene transfer mediated by intradermal injection of naked DNA was comparable in efficiency to electroporation. However, cellular distributions of the gene transfer of the two methods were different.