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

Virus- and nonvirus-mediated immunosuppressive cytokine gene therapy prolon gs cardiac allograft survival in various nonfunctional heart transplant ani mal models, but its cardiac adverse effects have not been addressed. Recent ly, 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-media ted ex vivo interleukin (IL)-10 gene transfer in functional donor hearts. T he efficiency of liposome-mediated gene transfer was greatly improved in ph ysiologically functioning donor hearts and was only three- to fourfold lowe r than adenovirus-mediated gene transfer. The efficacy of liposome-mediated IL-10 gene transfer was much higher than that mediated by adenovirus. Sign ificant negative inotropic and arrhythmogenic adverse effects on transplant ed hearts were observed due to viral cytotoxicity and immunogenesis, which greatly abated the therapeutic efficacy of this first generation adenovirus -mediated gene therapy.