We are investigating the use of ministrings to deliver toxic and therapeutic genes topoisomerases as a novel ovarian cancer gene therapy strategy. Toposiomerases modulate DNA topology by relaxing supercoils and controlling torsion in the DNA helix. They do so via transient cleavage of the DNA helix. Topoisomerase inhibitors or “poisons” include anthracyclines such as doxorubicin and daunorubicin and are common cancer chemotherapeutics. Topoisomerase poisons stabilize topoisomerase-mediated intermediates, leading to an accumulation of double-stranded DNA breaks, which in turn induces apoptosis or cell death. We aim to encode specific negative dominant mutant topoisomerase alleles that simulate the activity of toxic topoisomerase inhibitor-derived intermediates without the need for toxic topoisomerase poison addition.
We are also applying BEAM technology to the development of a novel targeted therapeutic vector against ovarian cancer.