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AssigneeUniversity of South Florida
InventorsDuane C. Eichler, Larry P. Solomonson, Laura C. Pendleton
Estimating the term…
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.
An isolated polynucleotide that targets an out-of-frame, upstream, overlapping open reading frame within the extended 5′-untranslated region (5′-UTR) of argininosuccinate sythase (AS), wherein said polynucleotide reduces expression of two messenger RNA molecules having initiation sites at nucleotide −92 and nucleotide −66 relative to nucleotide 117 of SEQ ID NO:33.
Dependencies are inferred from the claim text.