GENE-THERAPY - ITS PRESENT AND FUTURE IN DERMATOLOGY

Gene therapy consists in the introduction of a gene in cells in order to make them producing the corresponding protein in vivo. Theorically, the aims of gene therapy are numerous: substitution of a deficient ge ne (by the introduction of a functionnal gene), inhibition of a gene u sing antisense oligonucleotides or ribozymes, introduction of an exoge nous gene encoding for a cytokine in order to enhance the immune respo nse against tumor antigens (''gene immunotherapy''), introduction of a ''suicide gene'' (which makes cells sensitive to cytotoxic drugs) and , finally, introduction of a ''toxic gene'' in order to kill cells in situ. Genes may be introduced into the patient himself (direct gene th erapy). They may be introduced using a two-steps procedure: introducti on of the gene, in vitro, in cells sampled from the patient and, then, introduction of these transducted cells into the patient (indirect ge ne therapy). Several methods are used to introduce a gene in cells, bu t viral (retroviruses or adenoviruses) vectors are the most frequently used. For different reasons, skin appears to be highly efficient for gene therapy development. Several tumor antigenes have been identified in melanoma cells, allowing the development of gene immunotherapy pro tocols; some of these protocols are now used to treat patients at late stages of the disease. Other dermatoses are also good candidates for a gene therapy: the genodermatoses in which keratin mutations have bee n identified (congenital epidermolysis), xeroderma pigmentosum, T-cell lymphomas, epitheliomas...