Engineering RNAi Adenovirus Silencing Expression (ERASE) of DNA Repair Proteins
pERASE and Ad-ERASE (Engineered RNAi Adenovirus Silencing Expression) are respectively a plasmid and replication competent and/or deficient adenoviral vector-based systems encoding small inhibitory ribonucleic acid (siRNA). This system is designed to inhibit specific protein expression of DNA repair factors, including DNA-PKcs, ATM, ATR to enhance radiation- and chemotherapy-mediated cell killing of human cells. The unique aspects of this invention include; conceptual targeting of DNA repair proteins for radiation and chemotherapy sensitization by an siRNA technique; the sequences of the encoding plasmids and their incorporation into an adenoviral vector for delivery. When human cancer cells are transduced with ERASE plasmids, there is a 90% reduction in target protein expression and resultant increase in cellular radiation and chemotherapy sensitivity. As such, this invention has the potential to substantial improve the results of radiation and chemotherapy for diseases that depend on these therapies to kill cells or to limit cellular growth potential. Description (Set) Proposed Use (Set) Ionizing radiation and chemotherapy are frequently employed in the treatment of many diseases, particularly cancer. Many cell types are relatively radiation or chemotherapy resistant, resulting in a diminished therapeutic outcome. This diminished outcome is particularly problematic in the treatment patients with cancer. As such, techniques that seek to increase radiation-induced and chemotherapy-induced killing of the targeted cells are necessary. ERASE directly addresses this goal by providing the means to substantially increase cell killing of targeted cells and, when applied to treatment of cancer, should increase cancer control. Patent (Set) WO 2004/043406
DeWeese, Theodore L.
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