This study was designed to develop adeno-associated virus (AAV)-based vectors that could down-regulate expression of specific viral genes by mediating the production of appropriate antisense RNA molecules. Among targets chosen for study are certain early viral gene products which are absolutely necessary for productive viral infection. A series of AAV-based vectors has been crated in which the endogenous AAV promoters and coding sequences were replaced with a polylinker and several strong constitutive and inducible heterologous promoters. An encapsidation system has been developed in order to produce high titres of infectious recombinant virus. The induction of resistance to both HIV-1 and HSV-1 infection by such vectors is currently being studied, and present results indicate that a 95% reduction in the replication of either viruses can be achieved. Methods used include: gene cloning, transfection of cells, radio- immunoprecipitation, immunofluorescence, RNA and DNA hybridization techniques.