GENE-THERAPY FOR INFECTIOUS-DISEASE - THE AIDS MODEL

Gene therapy could be used to introduce either a functional copy of an altered endogeneous gene into the target tissue or a foreign gene cod ing for a protein with anti-viral or anti-neoplastic properties. The a bsence of efficient therapeutic drugs makes AIDS one obvious candidate among the infectious diseases which might be treated by gene therapy. Since HIV predominantly infects cells of the hematopoietic system, pl uripotent stem cells constitute potential targets for the introduction of foreign antiI-HIV genes. Reimplantation of the genetically modifie d stem cells into AIDS patients Should theoretically allow the repopul ation of the host with mature CD4(+) cell populations expressing novel molecules that might interfere with viral replication and slow the pr ogression of the disease. Identification of efficient and safe antivir al genes is therefore a critical issue in the successfull development of an AIDS gene therapy protocol. Given the molecular complexity of HI V replication, it is important not to focus on a single antiviral gene therapy strategy but to test in parallel, both in vitro and in vivo, several approaches aimed at targeting multiple independent steps of th e viral replication cycle. While some of these strategies proved relat ively efficient in vitro, and several phase I clinical trials have alr eady been proposed, evidence for in vivo efficacy is still lacking for most of the approaches. This review describes the AIDS gene therapy s trategies currently under evaluation in various laboratories, with a p articular focus on their respective advantages and limitations.