Redox-Modulating Gene Therapies for Human Diseases

Baseline levels of reactive oxygen species (ROS) are generated as an integral component of cellular function. Under certain conditions, e.g., the presence of an elevated concentration of transition metal (Fe/Cu) ions, drug metabolism, or ischemia-reperfusion, ROS generation is exaggerated to an extent that overwhelms cellular antioxidant defenses and results in oxidative stress. Oxidative stress has been characterized by the assessment of oxidative damage to cellular components, e.g., protein, lipid, and nucleic acid. More recent studies have determined that at a concentration much below that required for inflicting oxidative damage, ROS may serve as cellular second messengers through the regulation of numerous signal transduction pathways. For this reason, much of the current medical focus in this area has been directed toward the understanding of redox-driven physiological and pathophysiological processes in the cell. The goal of such research is to formulate effective strategies for manipulating the cellular redox environment in a manner that is beneficial for restoring normal cell functions in the setting of disease.