Method for enhanced uptake of viral vectors in the myocardium
AssigneeCelladon Corporation
InventorKrisztina Maria Zsebo
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Abstract
The present invention relates to improved therapies for the treatment of heart disease, particularly the improved delivery of therapeutic agents to heart tissue by direct infusion into the coronary circulation. A preferred embodiment of the invention is a method comprising, identifying a mammal in need of treatment or prevention of heart disease, and supplying NO to the coronary circulation prior to, and/or during the infusion of a therapeutic polynucleotide into a blood vessel of the coronary circulation in vivo.
Claims12
A method of treating heart failure by transfecting cardiac cells of a human, the method comprising:
- identifying a human in need of treatment for heart failure;
- intravenously administering nitroglycerin to said human at an initial does of 10-20 μg/minute at least 25 minutes prior to administration of a therapeutic polynucleotide and continuing to intravenously administer nitroglycerin during administration of said therapeutic polynucleotide;
- and
- administering a therapeutic polynucleotide into a lumen of a coronary artery in vivo for at least about 10 minutes, wherein said coronary artery comprises the left coronary artery, the right coronary artery, or the left and right coronary artery;
- wherein a coronary circulation is not isolated or substantially isolated from a systemic circulation of the human, wherein said therapeutic polynucleotide comprises a SERCA2a coding sequence, said therapeutic polynucleotide is packaged in a DNAse resistant particle (DRP) of a AAV2/1 viral vector, and a total number of DRP infused into said lumen is not more than about 1×1014, and wherein said therapeutic polynucleotide transfects cardiac cells of said human resulting in the treatment of said heart failure.
Dependencies are inferred from the claim text.