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Ann Thorac Surg 1996;62:1669-1676
© 1996 The Society of Thoracic Surgeons
Division of Neurosurgery, Department of Surgery, New York Hospital-Cornell University Medical College, New York, New York; Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, New York; Somatix Therapy Corp, Alameda, California; Gene Therapy Center, University of North Carolina, Chapel Hill, North Carolina; Division of Endocrinology, Department of Medicine, and Division of Cardiothoracic Surgery, Department of Surgery, North Shore University Hospital, Manhasset, New York; New York University School of Medicine, New York, New York; and Arizona Heart Institute, Phoenix, Arizona
Accepted for publication July 25, 1996.
Background. Viral vector-mediated gene transfer into the heart represents a potentially powerful tool for studying both cardiac physiology as well as gene therapy of cardiac disease. We report here the use of a defective viral vector, which expresses no viral gene products, for gene transfer into the mammalian heart. Previous studies have used recombinant viral vectors, which retained viral genes and yielded mostly short-term expression, often with significant inflammation.
Methods. An adeno-associated virus vector was used that contains no viral genes and is completely free of contaminating helper viruses. The adeno-associated virus vector was applied to rat hearts by direct intramuscular injection; adeno-associated virus was also infused into pig hearts in vivo via percutaneous intraarterial infusion into the coronary vasculature using routine catheterization techniques.
Results. Gene transfer into rat heart yielded no apparent inflammation, and expression was observed for at least 2 months after injection. Infusion into pig circumflex coronary arteries resulted in successful transfer and expression of the reporter gene in cardiac myocytes without apparent toxicity or inflammation; gene expression was observed for at least 6 months after infusion.
Conclusions. We report the use of adeno-associated virus vectors in the cardiovascular system as well as successful myocardial gene transfer after percutaneous coronary artery infusion of viral vectors in a large, clinically relevant mammalian model. These results suggest that safe and stable gene transfer can be achieved in the heart using standard outpatient cardiac catheterization techniques.
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