EXPRESSION OF A PROTECTIVE GENE PROLONGS SURVIVAL OF T-CELLS IN HUMANIMMUNODEFICIENCY VIRUS-INFECTED PATIENTS

The resistance of acquired immunodeficiency syndrome (AIDS) to traditi onal drug therapy has prompted a search for alternative treatments for this disease, One potential approach is to provide genetic resistance to viral replication to prolong latency, This strategy requires the d efinition of effective antiviral genes that extend the survival of T c ells in human immunodeficiency virus (HIV)-infected individuals, We re port the results of a human study designed to determine whether a gene tic intervention can prolong the survival of T cells in HIV-infected i ndividuals, Gene transfer was performed in enriched CD4(+) cells with plasmid expression vectors encoding an inhibitory Rev protein, Rev M10 , or a deletion mutant control, Delta Rev M10, delivered by gold micro particles. Autologous cells separately transfected with each of the ve ctors were returned to each patient, and toxicity, gene expression, an d survival of genetically modified cells were assessed, Cells that exp ressed Rev M10 were more resistant to HIV infection than those with De lta Rev M10 in vitro, In HIV-infected subjects, Rev M10-transduced cel ls showed preferential survival compared to Delta Rev M10 controls, Re v M10 can therefore act as a specific intracellular inhibitor that can prolong T-cell survival in HIV-1-infected individuals and potentially serve as a molecular genetic intervention which can contribute to the treatment of AIDS.