Gene therapy in lung transplantation

Feasibility of ex vivo adenovirus-mediated gene transfer to the graft

Alain Chapelier, Claire Danel, Michel Mazmanian, Emile A. Bacha, Hassan Sellak, Marie Agnès Gilbert, Philippe Hervé, Patricia Lemarchand

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Lung transplantation is associated with complications such as reperfusion injury and graft rejection. Gene therapy targeted to the graft offers a promising approach to the prevention of these complications. Because adenovirus vectors can transfer genes in vivo to the lung vasculature, me evaluated the feasibility of adenovirus-mediated gene transfer to the lung graft in a porcine model of left lung allotransplantation. Following removal of the donor lung, an adenovirus vector encoding the β-galactosidase (β-Gal) gene was injected ex vivo into the lumen of the upper lobe pulmonary artery of the graft. After 2 hr of incubation at 10°C, the lung graft was implanted into the recipient animal. Three days later, the animals were sacrificed and the lung graft was evaluated for β-Gal activity. No β-Gal activity was detected in the left lower lobe used as a control. In contrast, β-Gal activity was detected in endothelial cells of the left upper lobe pulmonary circulation, and was also observed in airway and alveoli epithelial cells. However, less than 1% of cells of the graft expressed β-Gal. In vitro experiments showed that this may be explained in part by the low temperature and the short duration of adenovirus incubation within the graft, and by the low susceptibility of porcine cells to human adenovirus. Furthermore, expression of the exogenous gene occurred in several organs of recipient animals. Thus, adenovirus-mediated gene transfer to the lung graft is feasible ex vivo, but several parameters limit gene transfer efficiency and need to be improved before clinical application is attempted.

Original languageEnglish (US)
Pages (from-to)1837-1845
Number of pages9
JournalHuman Gene Therapy
Volume7
Issue number15
DOIs
StatePublished - Oct 1 1996

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Lung Transplantation
Adenoviridae
Genetic Therapy
Transplants
Lung
Genes
Swine
Galactosidases
Animal Structures
Human Adenoviruses
Pulmonary Circulation
Graft Rejection
Reperfusion Injury
Pulmonary Artery
Endothelial Cells
Epithelial Cells
Gene Expression
Temperature

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Chapelier, A., Danel, C., Mazmanian, M., Bacha, E. A., Sellak, H., Gilbert, M. A., ... Lemarchand, P. (1996). Gene therapy in lung transplantation: Feasibility of ex vivo adenovirus-mediated gene transfer to the graft. Human Gene Therapy, 7(15), 1837-1845. https://doi.org/10.1089/hum.1996.7.15-1837

Gene therapy in lung transplantation : Feasibility of ex vivo adenovirus-mediated gene transfer to the graft. / Chapelier, Alain; Danel, Claire; Mazmanian, Michel; Bacha, Emile A.; Sellak, Hassan; Gilbert, Marie Agnès; Hervé, Philippe; Lemarchand, Patricia.

In: Human Gene Therapy, Vol. 7, No. 15, 01.10.1996, p. 1837-1845.

Research output: Contribution to journalArticle

Chapelier, A, Danel, C, Mazmanian, M, Bacha, EA, Sellak, H, Gilbert, MA, Hervé, P & Lemarchand, P 1996, 'Gene therapy in lung transplantation: Feasibility of ex vivo adenovirus-mediated gene transfer to the graft', Human Gene Therapy, vol. 7, no. 15, pp. 1837-1845. https://doi.org/10.1089/hum.1996.7.15-1837
Chapelier, Alain ; Danel, Claire ; Mazmanian, Michel ; Bacha, Emile A. ; Sellak, Hassan ; Gilbert, Marie Agnès ; Hervé, Philippe ; Lemarchand, Patricia. / Gene therapy in lung transplantation : Feasibility of ex vivo adenovirus-mediated gene transfer to the graft. In: Human Gene Therapy. 1996 ; Vol. 7, No. 15. pp. 1837-1845.
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