This project is designed to test the feasibility of using radiolabeled nucleic acid probes as diagnostic and/or therapeutic radiopharmaceuticals. Such radiolabeled DNA probes can be used in an antisense fashion to interact with mRNA or in an antigene fashion via triplex binding to targeted genomic sequences of interest. In this second year of our project, we are focusing on exploiting radioiodine-labeled DNA probes in triplex-binding experiments. By labeling the probe with iodine-125, we have been able to study the use of an Auger-electron emitter to produce double-strand breaks in the targeted genomic DNA sequence. Auger-electron-emitting radionuclides deposit high doses of energy within 1 to 10 nm of the site of their decay and are thus well-suited for this approach to gene-targeted radiation therapy. We have successfully demonstrated intermolecular site-specific cleavage of duplex DNA by Auger electrons from the decay of iodine-125 delivered by a triplex- forming oligonucleotide. Future studies will expand upon this work to determine the precise radiobiology of these interactions.