Long-term antegrade epicardial coronary infusion of adeno-associated virus vector for gene therapy

摘要

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 the use of a therapeutic polynucleotide composition adapted to transfect cardiac cells in the preparation of a medicament for treating or preventing cardiac disease by infusing the polynucleotide into a blood vessel of the coronary circulation over a period of at least three minutes, without isolating the coronary circulation from the systemic circulation. In a further preferred embodiment, the polynucleotide comprises a SERCA2a coding sequence packaged in a DNase resistant particle (DNP) of an AAV2/1 viral vector, the total number of DRP infused is less than or equal to 1 x 10 13 , and the blood vessel is the right or left coronary artery.