Abstract
Gene therapy holds great promise as a targeted treatment of cardiovascular diseases, which remain a major cause of morbidity and mortality in contemporary societies. Selection of the appropriate vector delivery method is critical for efficient transduction in the myocardium. Direct myocardial delivery is a feasible and effective method that has been shown to exhibit enhanced gene expression compared to coronary infusion and pericardial delivery. It is one of the most widely used gene transfer methods in both animal studies and clinical trials. The advantages, which result from a delivery that avoids exposure to the blood and bypasses the endothelial barrier, are a high local concentration at the injection site and a decreased leakage to off-target organs. The vectors are injected either with an endomyocardial or an epicardial approach, either surgically or percutaneously. In this chapter, we present the different approaches of direct myocardial injection, their advantages and their realization method in preclinical large animal models of cardiovascular diseases.
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Acknowledgments
This work is supported by NIH P50 HL112324, R01 HL119046, R01 HL117505, R01 HL128099, R01 HL129814, R01HL131404, & T32 HL007824 (R. J. H.), and a Transatlantic Leducq Foundation grant. We would like to acknowledge the Gene Therapy Resource Program (GTRP) of the National Heart, Lung, and Blood Institute, National Institutes of Health for providing some of the gene vectors used in these studies. G.B. was supported by the French Federation of Cardiology.
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Bonnet, G., Ishikawa, K., Hajjar, R.J., Kawase, Y. (2017). Direct Myocardial Injection of Vectors. In: Ishikawa, K. (eds) Cardiac Gene Therapy. Methods in Molecular Biology, vol 1521. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6588-5_17
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DOI: https://doi.org/10.1007/978-1-4939-6588-5_17
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