Vectorologie : orientations et progrès récents.

Abstract

En depit de l' imporlance des investissements et du foisonnement des projets de recherche, l' efficacite clinique de la therapie genique n' est toujours pas demontree. Des 1995, la direction des NIH (national institutes of health) aux Etats-Unis s' en est inquiete et a designe un comite charge d' analyser la situation. Dans son rapport (http://www.nih.gov/news/panelrep.html), le comite co-preside par Stuart Orkin et Arno Motulsky, reconnait la validite des concepts qui fondent la therapie genique mais souligne que les obstacles sont avant tout d' ordre fondamental. Les vecteurs de transfert de gene y sont designes comme l' element limitant principal. Aucun d' entre eux, qu il soit ou non derive de virus, ne presente l' efficacite et la securite requises pour une utilisation therapeutique chez l' homme Ainsi, le comite Orkin-Motulski preconise de revenir a une recherche fondamentale et technologique de haut niveau afin de developper des outils performants. En outre, le rapport insiste sur la necessite d 'approfondir l' etude des mecanismes physiopathologiques des maladies et de developper des modeles animaux.

Over the past few year, the field of gene therapy has placed a strong emphasis on vector research. This resulted from the outcome of the first series of clinical trials as well as from accumulated pre-clinical data. These collectively indicate that although the concept of gene therapy is valid, the tools we have in hand are far from being efficient enough. Three successive levels of problem exist. First, much fundamental investigation on the mechanism of gene transfer is needed and novel types of vectors have to be engineered. Second, the vector research must be linked to the development of optimised procedure for the production of reagents to be used in clinical trials. Finally, production facilities accessible to the scientific community must be organised. Here, we briefly describe the most significant progresses in viral vectors development (retroviruses, adenoviruses and adeno-associated viruses), and the current efforts designed to facilitate access to high quality vectors to investigators with a gene therapy project. [References: 13]