This is a proposal to create new aptamers to reverse transcriptase via SELEX and to characterize the interaction of these aptamers in detail. Novel approaches to generate chimeric aptamers will be used in the proposed studies and the interaction of these aptamers with RT will be evaluated through the use of several complementary biochemical and physical assays. In addition, experiments will be carried out to see what kinds of RT resistant mutants arise in response to various candidate aptamers.