The purpose of this research is to explore the use of nucleic acid probes as potential radiopharmaceuticals to be used in diagnostic and therapeutic applications, particularly in patients with cancer. The specificity of nucleic acid probes is being examined in anti-sense and triplex-binding formulations which are specifically radiolabelled as tracer or therapeutic radiopharmaceuticals. This group was established approximately one-year ago to explore the possibilities of using such agents to target specific genes and gene products. Two publications and two patent applications have resulted from the first year of work. These focus on the results from in vitro experiments using Auger-emitting radionuclides attached to DNA probes which target a DNA sequence and cause site-specific DNA damage within the region of the target sequence. The targeting is accomplished by triplex formation by the radiolabeled probe and duplex DNA target. An incorporated viral DNA sequence within the host genome was chosen for the first experiments in an intracellular model. Future work will examine chemical modifications of the nucleic acid probe to enhance stability in a triplex, effects of radiolabelling methods on probe stability and specificity, and in vivo delivery strategies.
