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j. Soc. Cosmet. Chem., 41, 85-92 (January/February 1990) Enhancement of DNA repair of UV damage in mouse and human skin by liposomes containing a DNA repair enzyme DANIEL B. YAROSH, JEANNIE TSIMIS, and VIVIEN YEE, Applied Genetics Inc., 205 Buffalo Avenue, Freeport, NY 11520. Received November 26, 1989. Presented at the Annual Meeting of the Society of Cosmetic Chemists, New York, December 7-8, 1989. Synopsis The DNA repair enzyme T4 endonuclease V was encapsulated in liposomes to enhance repair of pyrimidine dimers formed in DNA by UV. Addition of the liposornes to human epidermal keratinocytes in culture increased the removal of DNA damage, as measured by loss of endonuclease-sensitive sites, and enhanced DNA repair synthesis, as measured by an increase in unscheduled DNA synthesis. Topical treatment of UV-irradiated SKH-1 hairless mice with liposomes increased the removal of pyrimidine dimers from epi- dermal DNA. The results demonstrate that topical application of liposornes containing T4 endonuclease V may enhance DNA repair when applied in lotion either before or after UV exposure. INTRODUCTION Skin cancer caused by ultraviolet (UV) radiation has reached epidemic proportions in the United States (1). The most dramatic evidence of the link between UV and skin cancer comes from the human genetic disease xeroderma pigmentosum (XP). XP pa- tients have a biochemical defect in the repair of DNA damage caused by UV that causes a failure to remove photoproducts from their UV-irradiated DNA, leading to persistent DNA damage in skin and malignant transformation. Patients with XP develop solar damage and pigmentation abnormalities in childhood, and malignancies arise on sun- exposed skin at rates 4,800 times the frequency in the general population (2). Their life expectancy is 30 years less than the average. Repair of UV-induced pyrimidine dimers in epidermal DNA is a critical determinant of the incidence of UV-induced skin cancer in man. Excision repair requires: (a) recogni- tion and incision of the DNA strand containing damage (b) excision of the lesion (c) resynthesis of DNA using the complementary strand as the template and (d) sealing the mended region by DNA ligase. When repair occurs in normal skin, the rate of removal of DNA damage is saturated at doses that produce erythema (3). The rate-limiting step is the first one: recognition and incision of dimers. We have begun a research program to enhance human DNA repair of UV damage by delivering purified recombinant DNA repair enzymes to epidermal cells using lipo- 85