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Am J Physiol Heart Circ Physiol 281: H1433-H1441, 2001;
0363-6135/01 $5.00
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Vol. 281, Issue 3, H1433-H1441, September 2001

Efficiency, efficacy, and adverse effects of adenovirus- vs. liposome-mediated gene therapy in cardiac allografts

Luyi Sen1,2, Yoo-Sun Hong1, Haimin Luo2, Guanggen Cui1,2, and Hillel Laks1

1 Division of Cardiothoracic Surgery, Department of Surgery, and 2 Division of Cardiology, Department of Medicine, University of California Medical Center and University of California School of Medicine, Los Angeles, California 90095

Virus- and nonvirus-mediated immunosuppressive cytokine gene therapy prolongs cardiac allograft survival in various nonfunctional heart transplant animal models, but its cardiac adverse effects have not been addressed. Recently, we developed a functional heterotopic heart transplant model in rabbits. For the first time, we were able to systematically compare the efficiency, efficacy, and adverse effects of optimized adenovirus- and liposome-mediated ex vivo interleukin (IL)-10 gene transfer in functional donor hearts. The efficiency of liposome-mediated gene transfer was greatly improved in physiologically functioning donor hearts and was only three- to fourfold lower than adenovirus-mediated gene transfer. The efficacy of liposome-mediated IL-10 gene transfer was much higher than that mediated by adenovirus. Significant negative inotropic and arrhythmogenic adverse effects on transplanted hearts were observed due to viral cytotoxicity and immunogenesis, which greatly abated the therapeutic efficacy of this first generation adenovirus-mediated gene therapy.

heart transplantation; acute allograft rejection; adenovirus-mediated gene transfer; liposome-mediated gene transfer; interleukin-10


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