Gene therapy strategies for the treatment of pituitary tumours

Gene therapy can be defined as the introduction of therapeutic nucleic acids into cells with the aim of ameliorating or curing a disease. Initially, gene therapy paradigms focused on single-gene disorders. Recently, it has become apparent that potential therapeutic nucleic acids can be considered as drugs and as such could also be used for treating a variety of diseases (Verma & Somia 1997, Lowenstein 1997). With recent advances in gene transfer technology, gene therapy has become a reality, with more than 2100 patients currently undergoing clinical gene therapy trials (Marcel & Grausz 1997). Given the high expectations from this new therapeutic modality and in spite of the lack of conclusive evidence for its efficacy from the initial trials, very valuable information has been gained from the preclinical and clinical trials. There are two main methods for transferring therapeutic transgenes into affected tissues: transplantation of autologous cells genetically modified ex vivo and direct delivery of the therapeutic transgenes into the target tissue. As far as gene therapy methods are concerned, ex vivo methods are losing popularity in relation to in vivo approaches (59% of patients by December 1994, and 39% of patients by December 1995) (Marcel & Grausz 1997). Currently, there are two major approaches for transferring therapeutic genes into diseased cells: using viral and non-viral vectors. Viral vectors used for clinical gene therapy include retroviruses, herpes simplex type 1 viruses (HSV1), adenoassociated viruses (AAVs), lentiviruses and adenoviruses (Kozarsky & Wilson 1993, Verma & Somia 1997). Non-viral vectors include naked DNA, liposomes and DNA–protein complexes (Kay et al. 1997) (Table 1). The therapeutic potential of each approach needs to be evaluated individually, taking into account various factors, e.g. nature of the disease to be treated, desired duration of treatment, number and type of cells to be transduced, level of transgene expression required.