The present invention is based in part on the discovery that the upstream open reading frame (uORF) in the extended 5′-untranslated region (5′-UTR) argininosuccinate synthase (AS) mRNA species is functional, and when functional, limits overall AS expression as well as nitric oxide (NO) production. Thus, the extended 5′-UTR AS mRNA species is a mechanism for regulating AS expression and NO production, and provides a target for the treatment of pathophysiological conditions associated with vascular endothelial dysfunction and characterized by impairment of NO production, such as heart failure, hypertension, hypercholesterolemia, atherosclerosis, and diabetes.
Eichler, Duane C.; Solomonson, Larry P.; and Pendleton, Laura C., "Polynucleotides targeted against the extended 5′-UTR region of argininosuccinate synthase and uses thereof" (2010). USF Patents. 487.
University of South Florida