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J Thorac Cardiovasc Surg 2002;124:1130-1136
© 2002 The American Association for Thoracic Surgery

Cardiothoracic Transplantation (TX)

Intratracheal adenovirus-mediated gene transfer is optimal in experimental lung transplantation

From the Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Mo.

Supported by National Institutes of Health grants R01 HL41281 (Dr Patterson) and R01 HL56643 (Dr Mohanakumar). Dr Kanaan is supported by Individual NRSA Fellowship 1 F32 HL68401-01.

Received for publication Nov 13, 2001. Revisions requested Jan 7, 2002; revisions received Jan 23, 2002. Accepted for publication Feb 20, 2002. Address for reprints: G. Alexander Patterson, MD, One Barnes-Jewish Hospital Plaza, 3108 Queeny Tower, St Louis, MO 63110 (E-mail: pattersona{at}msnotes.wustl.edu).

Objective: Gene transfer to experimental lung grafts has been shown to reduce ischemia-reperfusion injury and acute rejection. The optimal delivery route should produce high lung expression with no inflammation and minimal systemic expression. The goal of this study was to determine the optimal gene transfer route for use in experimental lung transplantation.
Methods: F344 rats were injected with 2.9 x 10¹⁰ plaque-forming units of adenovirus vector encoding ß-galactosidase through intratracheal, intravenous, intraperitoneal, or intramuscular delivery routes and killed 48 hours later. Gene expression was measured by means of enzyme-linked immunosorbent assay.
Results: Intratracheal delivery produces significantly greater gene expression in the lung (75,350 ± 47,288 pg/100 µg of protein, P < .001 vs intravenous, intraperitoneal, and intramuscular routes) and minimal systemic expression (nonsignificant in serum, kidney, liver, spleen, and muscle vs that seen in control animals, P = .016 for heart). Immunohistochemistry staining showed ß-galactosidase expression in the bronchial epithelium of lungs transfected through the intratracheal route with mild inflammation.
Conclusions: Intratracheal gene transfer provides significant expression in the lung with mild to no inflammation and minimal systemic expression. This delivery strategy has tremendous potential in experimental lung transplant models to reduce ischemia-reperfusion injury and acute allograft rejection and should be investigated further.

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