Efficiency, efficacy, and adverse effects of adenovirus vs. liposome-mediated gene therapy in cardiac allografts.
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.
Sen
L
L
Division of Cardiothoracic Surgery, Department of Surgery, University of California Medical Center and University of California School of Medicine, Los Angeles, California 90095, USA. lsen@mednet.ucla.edu
Hong
Y S
YS
Luo
H
H
Cui
G
G
Laks
H
H
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000917:Antibody Formation; D004594:Electrophysiology; D015316:Genetic Therapy / Q000009:adverse effects* / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics; D006084:Graft Rejection / Q000235:genetics / Q000517:prevention & control*; D016027:Heart Transplantation / Q000379:methods / Q000502:physiology*; D007111:Immunity, Cellular; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000235:genetics; D008081:Liposomes; D023421:Models, Animal; D011817:Rabbits
D008081:Liposomes; D016753:Interleukin-10