TARGETED GENE-THERAPY

Melanin biosynthesis is limited to melanocytes partly as a consequence of transcriptional regulation of the enzymes involved in this pathway . Promoter sequences of these enzyme genes may be utilised to drive ex pression of complementary DNA coding for therapeutic genes so as to pr ovide transcriptional targeting. We have used the 5'-flanking sequence s of the murine tyrosinase or tyrosinase-related protein 1 (TRP-1) gen es to show that such transcriptional targeting can be achieved both in vitro and in vivo. Using IL-2 as an example of an immunostimulatory g ene and Herpes Simplex Virus thymidine kinase (HSVtk) as an example of a prodrug-activating gene we have shown, in murine model systems, tha t substantial anti-tumour effects can be achieved by targeted gene the rapy approaches, The stage now is set for initial clinical evaluations in human patients.