The purpose of this project is 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 anti- sense fashion to interact with mRNA or in an anti-gene fashion via triplex binding to targeted genomic sequences of interest. In this first year of our project we have chosen to focus on exploiting radioiodine labeled DNA probes for use 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-emitting radionuclides deposit high doses of energy within 1 to 10 nm from 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 125-Iodine delivered by a triplex-forming oligonucleotide. Future studies will expand upon this work.