High-throughput, automated selection methods will be employed by the Ellington lab at the University of Texas at Austin to generate aptamers against HIV-1 Rev, Tat, reverse transcriptase, Rnase H, and the RRE. Aptamers will be characterized by the company Accacia, and subsequently assayed in cell culture models of viral infection by the Prasad lab at the Albert Einstein College of Medicine, as well as in animal models by the Johnson lab at Harvard. The selected aptamers will also be used to generate chips for mapping epitopes and for the detection of resistance mutants. The development of viral resistance will be further addressed by conducting re-selections against proteins that have acquired resistance mutations. Ultimately, these selection experiments should potentiate the development of highly efficacious gene therapies for AIDS and will also provide unique insights into the evolution of viral resistance.