14 Targets for Gene Therapy

Abstract

THE MEDICAL NEED FOR GENE THERAPY
Human gene therapy can be defined as the directed expression of exogenous genes or other nucleotide sequences for the purpose of correcting a disease-causing mutation and thereby modifying a disease or other phenotype. This revolutionary new approach to treatment has been fueled by the explosive growth of molecular and cellular genetics and to a lesser extent by our improved understanding of disease pathophysiology (Orkin and Williams 1988; Anderson 1992; Friedmann 1992, 1997; Weatherall 1995). The concept of gene therapy is the logical extension of this evolving knowledge, and, after an initial period of uncertainty and contention (Fletcher 1983a,b; Rifkin 1985; Walters 1986), there is now broad acceptance of the underlying scientific concepts. Its implementation toward clinical reality has been much more difficult than the establishment of the concept itself (see http://www.nih.gov/news/panelrep.html).

This novel approach to the therapy of human disease is based on the realization that previous medical treatments have usually been directed at the consequences of causative defects or at disease symptoms rather than at the underlying causes. All doctors realize that our approaches of treating many human diseases often fall short in bringing about definitive and permanent disease correction. Even therapies for the monogenic inborn errors of metabolism that are based on elegant modern biochemical and cellular knowledge often are inadequate when applied to real patients with real diseases (Treacy et al. 1995). For most human disease, there remains a deep conceptual and temporal gulf between an understanding of disease pathogenesis and...