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Gene therapy for barrett's esophagus: adenoviral gene transfer in different intestinal models

Cancer Gene Therapy volume 12, pages 778–786 (2005)Cite this article

Abstract

Adenoviral gene therapy could potentially be used for treatment of patients with a Barrett's esophagus. In order to study the feasibility of this approach it is important to study adenoviral intestinal transduction both in vitro and in vivo. In the present study, we used differentiating Caco-2 cells, closed intestinal loops and a Barrett's esophagus rat model to test transduction of adenoviruses expressing green fluorescent protein. We observed a decreased adenoviral transduction from 18.6 to 2.3% in undifferentiated and differentiated Caco-2 cells, respectively. This could be improved by the use of the mucolytic agent N-acetylcysteine (NAC) and the polycation diethylaminoethyl-dextran (DEAE-dextran), which improved transduction in differentiated cells five- and ten-fold, respectively. Also an RGD-retargeted adenovirus showed an improved transduction in differentiated cells. In closed intestinal loops adenoviral transduction was limited and the use of NAC and DEAE-dextran or RGD targeting had little effect. The Barrett's esophagus rat model consisted of an esophagojejunostomy, which results in a Barrett's esophagus and esophageal tumors within 6 months. Adenoviral transduction in this model was limited and mainly localized in the basal layer of normal esophagus and stromal tissue of a Barrett's segment. We conclude that although the adenovirus shows promising results in vitro, the current adenoviral vectors are probably not suitable for patients with Barrett's esophagus.

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Authors and Affiliations

  1. AMC Liver Center, Academic Medical Center, Amsterdam, The Netherlands

    Willem A Marsman, Christianne J Buskens, John G Wesseling & Piter J Bosma

  2. Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands

    Willem A Marsman, Christianne J Buskens & J Jan B Van Lanschot

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  1. Willem A Marsman
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  2. Christianne J Buskens
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  3. John G Wesseling
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Correspondence to Willem A Marsman.

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Marsman, W., Buskens, C., Wesseling, J. et al. Gene therapy for barrett's esophagus: adenoviral gene transfer in different intestinal models. Cancer Gene Ther 12, 778–786 (2005). https://doi.org/10.1038/sj.cgt.7700841

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