A REVIEW OF CURRENT BASIC APPROACHES TO GENE-THERAPY

Over the past decade methods for delivering genes into mammalian cells aimed at subsequent expression of the transferred sequences from the host cell have been developped. Potential therapeutic applications hav e been envisaged and have raised great interest. Though procedures bas ed on gene targeting will not enter clinical protocols prior to the so lving of fundamental issues, procedures based on gene addition are cur rently underway. The expected benefit of genetic modification of somat ic cells needs to be carefully assessed and confronted to its potentia l risks. Whatever the technological strategy, non-propagation and non- transmission of the gene transfer delivery system is mandatory. Precli nical studies covering a large range of pathologies are currently unde rway; primarily aimed at demonstrating rather the technological feasib ility of various approaches than true therapeutic efficacy. Technologi cal improvements and the solving of basic issues dealing with both the regulation of gene expression and the biology of cell transplantation are still required in order for gene therapy to enter a phase of clin ical efficacy. Pluridisciplinarity only will allow for fruitful exchan ges between investigators in the basic sciences and therapists. This h as been the basis for creating a European Working group on human Gene Transfer and therapy (EWGT). Whatever the interest raised by gene ther apy and its innovatory potential, the relevance of this approach shoul d carefully be considered 1st) in terms of economical constraints and ethics; 2nd) in the context of an overall therapeutic strategy, in par ticular in the case of acquired disease like cancer, and confronted to alternative treatments such as targeted drugs.