TY - JOUR
T1 - Conditions of vector delivery improve efficiency of adenoviral-mediated gene transfer to the transplanted heart
AU - Yap, John
AU - Pellegrini, Carlo
AU - O'Brien, Timothy
AU - Tazelaar, Henry D.
AU - McGregor, Christopher G.A.
N1 - Funding Information:
This work was supported by grants from the Mayo Clinic and Foundation and the Bruce and Ruth Rappaport Program in Vascular Biology. The skillful technical assistance of Sharon Guy is gratefully acknowledged. This work is supported by grants from Mayo Clinic and Foundation. J. Yap is supported by a grant from HN Tjia Education Fund.
PY - 2001
Y1 - 2001
N2 - Objectives: Conditions for ex vivo gene transfer to the transplanted heart were studied in a model of syngeneic abdominal heterotopic heart transplantation in the rat. Various methods of adenoviral-mediated gene transfer to the transplanted heart were compared. Methods: In the first experiment, a dose response study, an adenoviral vector encoding the β-galactosidase gene was infused into the donor heart with the pulmonary artery open and flushed out prior to performing the transplant. In the second experiment, the effects of clamping the pulmonary artery during vector infusion and not flushing out the viral solution, resulting in vector dwell during the warm ischemia, were examined. Results: In the first experiment, gene transfer was relatively inefficient; however, transgene expression improved with increases in the vector dose (range, 1×107-1×109). The efficiency of gene transfer was significantly greater when the conditions of the second experiment were applied. In all models studied, cardiomyocytes and not vascular endothelial cells were the predominant cell type transduced. Conclusions: This study indicates that the conditions of adenoviral vector delivery are critical for optimizing gene transfer in the transplant setting. In addition, intravascular administration of adenoviral vector to the donor heart results predominantly in cardiomyocyte transgene expression.
AB - Objectives: Conditions for ex vivo gene transfer to the transplanted heart were studied in a model of syngeneic abdominal heterotopic heart transplantation in the rat. Various methods of adenoviral-mediated gene transfer to the transplanted heart were compared. Methods: In the first experiment, a dose response study, an adenoviral vector encoding the β-galactosidase gene was infused into the donor heart with the pulmonary artery open and flushed out prior to performing the transplant. In the second experiment, the effects of clamping the pulmonary artery during vector infusion and not flushing out the viral solution, resulting in vector dwell during the warm ischemia, were examined. Results: In the first experiment, gene transfer was relatively inefficient; however, transgene expression improved with increases in the vector dose (range, 1×107-1×109). The efficiency of gene transfer was significantly greater when the conditions of the second experiment were applied. In all models studied, cardiomyocytes and not vascular endothelial cells were the predominant cell type transduced. Conclusions: This study indicates that the conditions of adenoviral vector delivery are critical for optimizing gene transfer in the transplant setting. In addition, intravascular administration of adenoviral vector to the donor heart results predominantly in cardiomyocyte transgene expression.
KW - Adenovirus
KW - Gene therapy
KW - Gene transfer
KW - Heart
KW - Transplantation
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U2 - 10.1016/S1010-7940(01)00673-X
DO - 10.1016/S1010-7940(01)00673-X
M3 - Article
C2 - 11343956
AN - SCOPUS:0035004872
SN - 1010-7940
VL - 19
SP - 702
EP - 707
JO - European Journal of Cardio-Thoracic Surgery
JF - European Journal of Cardio-Thoracic Surgery
IS - 5
ER -