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British Medical Bulletin 51:647-655 (1995)
© 1995 The British Council

research-article

Targeted gene therapy

I R Hart1 and R G Vile2

1Richard Dimbleby Department of Cancer Research, Rayne Institute, St Thomas' Hospital London, UK
2ICRF Laboratory of Cancer Gene Therapy, Rayne Institute, St Thomas' Hospital London, UK

Abstract

Melanin biosynthesis is limited to melanocytes partly as a consequences of transcriptional regulation of the enzymes involved in this pathway. Promoter sequences of these enzyme genes may be utilised to drive expression of complementary DNA coding for therapeutic genes so as to provide trnascriptional targeting. We have used 5'-flanking sequences of the murine tyrosinase or tyrosinase-related protein 1 (TRO-1) genes to show that such transcriptional targeting can be acheived both in vitro and in vivo. Using IL-2 as an example of an immunostimulatory gene and Herpes Simplex Virus thymidine kinase (HSVtk) as an example of a prodrug-activating gene we have shown, in murine model systems, that substantial anti-tumour effects can be achieved by targeted gene therapy approaches. The stage now is set for initial clinical evaluations in human patients.


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