eNOS mutations useful for gene therapy and therapeutic screening
AssigneeYale University
InventorWilliam C. Sessa
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Abstract
The present invention relates to new NOS variants or mutants which contain structural alterations in the site of Akt dependent phosphorylation. The altered NOS proteins or peptides, especially the human eNOS proteins or peptides, Akt proteins or polypeptides and their encoding nucleic acid molecules are useful as gene therapy agents for the treatment of diseases including post angioplasty restenosis, hypertension, atherosclerosis, heart failure, diabetes and diseases with defective angiogenesis. NOS proteins and peptides are also useful in methods of screening for agents which modulate NOS activity.
Claims5
An isolated nucleic acid molecule encoding a variant of the endothelial nitric oxide synthase (eNOS) polypeptide of SEQ ID NO:3, wherein said variant is selected from the group consisting of a constitutively active nitric oxide synthase (NOS) polypeptide, a NOS polypeptide having an increased rate of nitric oxide (NO) production, and a NOS polypeptide having an increased reductase activity when compared with the wild-type NOS polypeptide of SEQ ID NO:3, wherein said variant consists of an amino acid mutation at the amino acid S of the consensus sequence motif RXRXXS/T.
Dependencies are inferred from the claim text.