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A Novel Method for Gene Transfer into Keratinocytes in Vivo

Sawamura et al (p. 195) show that the use of the hemagglutinating virus of Japan (HVJ) incorporated into liposomes is useful for in vivo gene transfer into normal and transformed keratinocytes. This method involves the entrapment of DNA and nuclear protein within liposomes and the use of HVJ to enhance liposome fusion with cell membranes, increasing the efficiency of gene transfer. This method has been used successfully for gene transfer in other cells and tissues, leading the investigators to ask whether this method might transfer genes effectively to epidermal keratinocytes in vivo. The authors introduced the beta-galactosidase gene into the skin of hairless rats by this method and detected enzyme activity in the keratinocytes of the treated skin. Transfer efficiency of the HVJ-liposome method was about five times higher than with the use of “naked” DNA. The authors also assessed the efficacy of the method for transfer of the thymidine kinase gene of herpes simplex virus, incorporation of which can cause inhibition of growth of squamous cell carcinoma cells incubated with ganciclovir. Growth of transfected tumor cells in the presence of ganciclovir was inhibited, indicating that the method was effective in this setting as well. These findings indicate that the HVJ-liposome method is suitable for gene transfer to keratinocytes in vivo as well as in vitro and could be useful in gene therapy.



Journal of Investigative Dermatology


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