In HIV infected cells, the interaction of Rev Responsive Element (RRE) with the viral protein Rev facilitates nucleo-cytoplasmic viral RNA transport. Successful prevention of this process can disrupt the viral life cycle. Using phage display techniques, zinc finger proteins were generated to bind specifically to RREIIB, the high affinity Rev binding site. Localization of the zinc finger binding was determined by NMR to be the initial Rev binding site on the RNA. In addition, the binding orientation of the protein was determined by paramagnetic shift mapping. The interaction of this designed zinc finger protein to the RREIIB RNA has been evaluated by various biophysical methods. Isothermal titration calorimetry was utilized to shed light on the energetics of the RREIIB – Zinc finger binding. NMR and gels shift assays were also employed to confirm and supplement ITC data. Various protein mutants were designed to determine the contribution / importance of individual side chains to the RNA binding affinity. The structure of the RNA-protein complex is being studied by conventional NMR methodology to provide further insight into RNA-protein interactions and refine the RNA binding activity of these proteins.