Abstract: In various aspects and embodiments, the invention provides a method of treating a cardiovascular disease in a subject in need thereof, the method comprising administering an effective amount of a viral vector comprising a therapeutic polynucleotide directly into the heart of the subject. In various embodiments, the pharmaceutical composition is administered through a series of 15 injections at separate delivery sites in the heart of the subject, and wherein the viral vector diffuses through substantially all of the heart.