Compositions for enhanced uptake of viral vectors in the...

A - Human Necessities – 61 – K

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A61K 48/00 (2006.01) C12N 15/864 (2006.01)

Patent

CA 2715765

The present invention relates to improved therapies for the treatment of heart disease, particularly the improved de-livery of therapeutic agents to heart tissue by direct infusion into the coronary circulation. A preferred embodiment of the inven-tion is a method of treating or preventing a cardiovascular disease by transfecting cardiac cells of a large mammal, the method comprising, identifying a mammal in need of treatment or prevention of heart disease, 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, where the therapeutic polynucleotide is infused into the blood vessel over a period of at least about three minutes, where the coronary circulation is not isolated or substantially isolated from the systemic circulation of the mammal; and where the therapeutic polynu-cleotide transfects cardiac cells of the animal resulting in the treatment or prevention of the heart disease.

La présente invention concerne des thérapies améliorées pour le traitement de maladies cardiaques, notamment la délivrance améliorée dagents thérapeutiques aux tissus cardiaques par perfusion directe dans la circulation coronaire. Un mode de réalisation préféré de linvention est un procédé de traitement ou de prévention dune maladie cardiovasculaire par transfection de cellules cardiaques dun mammifère de grande taille. Le procédé comprend lidentification dun mammifère ayant besoin dun traitement ou dune prévention dune maladie cardiaque, lintroduction de NO dans la circulation coronaire avant et/ou pendant la perfusion dun polynucléotide thérapeutique dans un vaisseau sanguin de la circulation coronaire in vivo. Selon linvention, le polynucléotide thérapeutique est perfusé dans le vaisseau sanguin pendant une durée dau moins environ trois minutes, la circulation coronaire nest pas isolée ou sensiblement isolée de la circulation systémique du mammifère, et le polynucléotide thérapeutique transfecte des cellules cardiaques de lanimal, ce qui permet le traitement ou la prévention de la maladie cardiaque.

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