Principles of gene therapy: prospects for the treatment of head and neck cancer.

Few areas of research have raised as much interest and introspection, not to mention false hopes, as gene therapy. Indeed, few areas can have induced the editorial writers to wax quite so lyrical (Verma, 1994; Leiden, 1995; Blau et al., 1997). The possibility of using DNA as a therapeutic tool first became theoretically feasible as a result of the advances in recombinant DNA technology which have revolutionized biological research in the last two decades. With the isolation and cloning of the genes responsible for inherited monogenetic disorders such as cystic fibrosis (Riordan et al., 1989; Rommens et al., 1989), Lesch-Nyhan syndrome (Brennand et al., 1983; Melton et al., 1984) and adenosine deaminase (ADA)-deficient severe combined immune deficiency (SCID) (Orkin et al., 1983) theoretical cures could be achieved by the introduction and expression of a normal functional copy of the faulty gene in the appropriate tissue. However, the practical requirements for such gene therapy to be successful are formidable. After the gene has been isolated, its regulatory sequences must also be identified to ensure that expression of the transgene occurs in the appropriate tissue and at the appropriate time. Secondly, practical ways have to be found of delivering the gene to the appropriate organ and, finally, once expression is achieved, it must continue indefinitely, to obviate the requirement for multiple and repeated treatments. Perhaps not surprisingly, initial clinical trials of gene therapy in cystic fibrosis (Knowles et al., 1995) and ADAdeficient SCID (Blaese et al., 1995) have met with very limited success.