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AssigneeDuke University
InventorsWalter J. Koch, Robert J. Lefkowitz, Carmelo A. Milano, Howard A. Royman
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The present invention deals with gene therapy for treating chronic heart failure and other cardiac disease states which are accompanied by a reduced number or functioning of myocardial beta-adrenergic receptors (β-AR). β-AR receptor function is augmented in transgenic animals by delivery and expression of a beta-2-adrenergic receptor gene or a gene encoding a beta adrenergic receptor kinase inhibitor, resulting in increased in vivo left ventricular function. The present invention includes recombinant plasmid vectors, alternative beta-adrenergic receptor gene delivery strategies, and transgenic mice carrying a β-AR transgene, a β-ARK transgene, or a β-ARK inhibitor transgene.
A method of inhibiting the activity of a beta adrenergic receptor kinase 1 (βARK1) so as to improve myocardial function in a mammal, comprising administering to the cardiac muscle of said mammal via cardiac perfusion an effective amount of an expression vector comprising a promoter active in myocardium operably linked to a DNA sequence encoding a βARK1 inhibitor, wherein said inhibitor comprises a βARK1 carboxyl terminal sequence comprising βARK1 residues Trp643 to Ser670 (SEQ ID NO:1), and wherein expression of said βARK1 inhibitor results in an increase in myocardial function.
A method of inhibiting the activity of a beta adrenergic receptor kinase 1 (βARK1) so as to improve myocardial function in a mammal, comprising administering directly to the cardiac muscle of said mammal an effective amount of an expression vector comprising a promoter active in myocardium operably linked to a DNA sequence encoding a βARK1 inhibitor, wherein said inhibitor comprises a βARK1 carboxyl terminal sequence comprising βARK1 residues Trp643 to Ser670 (SEQ ID NO:1), and wherein expression of said βARK1 inhibitor results in an increase in myocardial function.
Dependencies are inferred from the claim text.