The present invention relates to therapies for the treatment of cardiovascular diseases, particularly the delivery of therapeutic agents to heart tissue by direct infusion into the coronary circulation. A preferred embodiment of the invention is a method of treating or preventing a cardiovascular disease by transfecting cardiac cells of a large mammal, the method comprising, identifying an mammal in need of treatment or prevention of a cardiovascular disease, infusing 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 polynucleotide transfects cardiac cells of the animal resulting in the treatment or prevention of the cardiovascular disease.
