The scope of gene therapy in humans: scientific, safety and ethical considerations

Gene therapy entails the introduction of specific, functional genes into cells for therapeutic or preventive purposes. Therapeutic genes may be introduced into cells in vitro (and the treated cells then introduced into the patient) or directly in vivo. Gene therapy may be used for several purposes including: (a) Gene replacement in genetic diseases; (b) Destroying malignant cells in neoplastic diseases; (c) Modifying immune responses; (d) Providing trophic molecules; (e) Immunisation against infectious diseases. In designing gene therapy strategies the following major items need to be investigated and optimised: (1) Relevant biological characteristics of the treatable cells and tissues; (2) Gene vectors (viral or non-viral); (3) The gene expression cassette (promoter+cDNA+poly A signal); (4) The safest and most effective route of administration; (5) Longevity of the transgene expression. Before human trials for gene therapy can commence for a given disease, extensive preclinical studies are to be carried out in an appropriate experimental models to assure the feasibility, safety and efficiency of the enterprise. For each disease or application, the risk/benefit ratio must be determined. Permission by regulatory agencies, institutional review boards (IRB) and thorough informed consent are essential. Although gene therapy holds great promise for many human diseases, it is still too early to predict the extent and timetable of its successful implementation in individual diseases.