Conditions of vector delivery improve efficiency of adenoviral-mediated gene transfer to the transplanted heart

John Yap, Carlo Pellegrini, Timothy O'Brien, Henry D. Tazelaar, Christopher G A McGregor

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)702-707
Number of pages6
JournalEuropean Journal of Cardio-thoracic Surgery
Volume19
Issue number5
DOIs
Publication statusPublished - 2001

Fingerprint

Genes
Transgenes
Cardiac Myocytes
Pulmonary Artery
Galactosidases
Heterotopic Transplantation
Transplants
Warm Ischemia
Heart Transplantation
Constriction
Endothelial Cells

Keywords

  • Adenovirus
  • Gene therapy
  • Gene transfer
  • Heart
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Conditions of vector delivery improve efficiency of adenoviral-mediated gene transfer to the transplanted heart. / Yap, John; Pellegrini, Carlo; O'Brien, Timothy; Tazelaar, Henry D.; McGregor, Christopher G A.

In: European Journal of Cardio-thoracic Surgery, Vol. 19, No. 5, 2001, p. 702-707.

Research output: Contribution to journalArticle

Yap, John ; Pellegrini, Carlo ; O'Brien, Timothy ; Tazelaar, Henry D. ; McGregor, Christopher G A. / Conditions of vector delivery improve efficiency of adenoviral-mediated gene transfer to the transplanted heart. In: European Journal of Cardio-thoracic Surgery. 2001 ; Vol. 19, No. 5. pp. 702-707.
@article{f5059d1e95454988a497503039d9f2df,
title = "Conditions of vector delivery improve efficiency of adenoviral-mediated gene transfer to the transplanted heart",
abstract = "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.",
keywords = "Adenovirus, Gene therapy, Gene transfer, Heart, Transplantation",
author = "John Yap and Carlo Pellegrini and Timothy O'Brien and Tazelaar, {Henry D.} and McGregor, {Christopher G A}",
year = "2001",
doi = "10.1016/S1010-7940(01)00673-X",
language = "English",
volume = "19",
pages = "702--707",
journal = "European Journal of Cardio-thoracic Surgery",
issn = "1010-7940",
publisher = "European Association for Cardio-Thoracic Surgery",
number = "5",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=0035004872&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035004872&partnerID=8YFLogxK

U2 - 10.1016/S1010-7940(01)00673-X

DO - 10.1016/S1010-7940(01)00673-X

M3 - Article

VL - 19

SP - 702

EP - 707

JO - European Journal of Cardio-thoracic Surgery

JF - European Journal of Cardio-thoracic Surgery

SN - 1010-7940

IS - 5

ER -