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 developed. Potential therapeutic applications have been envisaged and have raised great interest. Though procedures based on gene targeting will not enter clinical protocols prior to the solving of fundamental issues, procedures based on gene addition are currently underway. The expected benefit of genetic modification of somatic cells needs to be carefully assessed and confronted to its potential risks. Whatever the technological strategy, non-propagation and non-transmission of the gene transfer delivery system is mandatory. Preclinical studies covering a large range of pathologies are currently underway; primarily aimed at demonstrating rather the technological feasibility of various approaches than true therapeutic efficacy. Technological 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 clinical efficacy. Pluri-disciplinarity only will allow for fruitful exchanges between investigators in the basic sciences and therapists. This has been the basis for creating a European Working group on human Gene Transfer and therapy (EWGT). Whatever the interest raised by gene therapy and its innovatory potential, the relevance of this approach should carefully be considered 1st) in terms of economical constraints and ethics; 2nd) in the context of an overall therapeutic strategy, in particular in the case of acquired disease like cancer, and confronted to alternative treatments such as targeted drugs.