A novel method for gene delivery and expression in esophageal epithelium with fibrin glues containing replication-deficient adenovirus vector

Fuminori Teranishi, T. Umeoka, T. Saito, T. Tsukagoshi, N. Tanaka, Toshiyoshi Fujiwara

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Gene transfer to the esophageal epithelium holds the potential for the therapy of malignant as well as premalignant lesions in the upper gastrointestinal tract. Replication-deficient recombinant adenoviruses represent an efficient means of introducing genes in vivo into cells in a variety of organs. The majority of in vivo studies utilize direct submucosal injection for delivery of the viral vectors into the locoregional area of the gut; transferring genes into epithelial cells, however, is difficult because viruses are retained in the subepithelial space. To establish the efficient method for gene transfer into the epithelial cells, we have developed a multiluminal spray catheter that can be passed through the accessory channel of an endoscope, and we have evaluated the feasibility of fibrin glues as a vehicle of recombinant adenoviruses in a porcine model. Methods: The fibrinogen solution and the thrombion solution containing an E1/E3 deleted recombinant adenovirus expressing the bacterial lacZ gene (Ad-lacZ) were endoscopically sprayed on the porcine esophagus through the catheter attached to the dual-barrel syringe. Twenty-four hours after gene delivery, β -galactosidase activity of the esophagus was determined under the microscope following X-gal staining. Results: The fibrin glue could be locally sprayed on the porcine esophagus by using the multichannel catheter through the endoscope. Attachment of the fibrin glue comtining Ad-lacZ caused strong β-galactosidase staining on epithelial cells in the mucosal surface, but not in the basal cell layer. Conclusion: Endoscopic local delivery of recombinant adenoviruses in aerosolized fibrin glues through a multiluminal catheter could provide an optimal technique for gene transfer into epithelial cells in the mucosal surfece, which may have important implications for the treatment of human esophageal premalignant diseases.

Original languageEnglish
Pages (from-to)1845-1848
Number of pages4
JournalSurgical Endoscopy and Other Interventional Techniques
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 2003

Fingerprint

Fibrin Tissue Adhesive
Adenoviridae
Epithelium
Gene Expression
Catheters
Epithelial Cells
Galactosidases
Esophagus
Swine
Endoscopes
Genes
Esophageal Diseases
Staining and Labeling
Bacterial Genes
Gene Transfer Techniques
Upper Gastrointestinal Tract
Lac Operon
Syringes
Fibrinogen
Viruses

Keywords

  • Adenovirus vector
  • Esophageal epithelium
  • Fibrin glue
  • Gene delivery

ASJC Scopus subject areas

  • Surgery

Cite this

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title = "A novel method for gene delivery and expression in esophageal epithelium with fibrin glues containing replication-deficient adenovirus vector",
abstract = "Background: Gene transfer to the esophageal epithelium holds the potential for the therapy of malignant as well as premalignant lesions in the upper gastrointestinal tract. Replication-deficient recombinant adenoviruses represent an efficient means of introducing genes in vivo into cells in a variety of organs. The majority of in vivo studies utilize direct submucosal injection for delivery of the viral vectors into the locoregional area of the gut; transferring genes into epithelial cells, however, is difficult because viruses are retained in the subepithelial space. To establish the efficient method for gene transfer into the epithelial cells, we have developed a multiluminal spray catheter that can be passed through the accessory channel of an endoscope, and we have evaluated the feasibility of fibrin glues as a vehicle of recombinant adenoviruses in a porcine model. Methods: The fibrinogen solution and the thrombion solution containing an E1/E3 deleted recombinant adenovirus expressing the bacterial lacZ gene (Ad-lacZ) were endoscopically sprayed on the porcine esophagus through the catheter attached to the dual-barrel syringe. Twenty-four hours after gene delivery, β -galactosidase activity of the esophagus was determined under the microscope following X-gal staining. Results: The fibrin glue could be locally sprayed on the porcine esophagus by using the multichannel catheter through the endoscope. Attachment of the fibrin glue comtining Ad-lacZ caused strong β-galactosidase staining on epithelial cells in the mucosal surface, but not in the basal cell layer. Conclusion: Endoscopic local delivery of recombinant adenoviruses in aerosolized fibrin glues through a multiluminal catheter could provide an optimal technique for gene transfer into epithelial cells in the mucosal surfece, which may have important implications for the treatment of human esophageal premalignant diseases.",
keywords = "Adenovirus vector, Esophageal epithelium, Fibrin glue, Gene delivery",
author = "Fuminori Teranishi and T. Umeoka and T. Saito and T. Tsukagoshi and N. Tanaka and Toshiyoshi Fujiwara",
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T1 - A novel method for gene delivery and expression in esophageal epithelium with fibrin glues containing replication-deficient adenovirus vector

AU - Teranishi, Fuminori

AU - Umeoka, T.

AU - Saito, T.

AU - Tsukagoshi, T.

AU - Tanaka, N.

AU - Fujiwara, Toshiyoshi

PY - 2003/11

Y1 - 2003/11

N2 - Background: Gene transfer to the esophageal epithelium holds the potential for the therapy of malignant as well as premalignant lesions in the upper gastrointestinal tract. Replication-deficient recombinant adenoviruses represent an efficient means of introducing genes in vivo into cells in a variety of organs. The majority of in vivo studies utilize direct submucosal injection for delivery of the viral vectors into the locoregional area of the gut; transferring genes into epithelial cells, however, is difficult because viruses are retained in the subepithelial space. To establish the efficient method for gene transfer into the epithelial cells, we have developed a multiluminal spray catheter that can be passed through the accessory channel of an endoscope, and we have evaluated the feasibility of fibrin glues as a vehicle of recombinant adenoviruses in a porcine model. Methods: The fibrinogen solution and the thrombion solution containing an E1/E3 deleted recombinant adenovirus expressing the bacterial lacZ gene (Ad-lacZ) were endoscopically sprayed on the porcine esophagus through the catheter attached to the dual-barrel syringe. Twenty-four hours after gene delivery, β -galactosidase activity of the esophagus was determined under the microscope following X-gal staining. Results: The fibrin glue could be locally sprayed on the porcine esophagus by using the multichannel catheter through the endoscope. Attachment of the fibrin glue comtining Ad-lacZ caused strong β-galactosidase staining on epithelial cells in the mucosal surface, but not in the basal cell layer. Conclusion: Endoscopic local delivery of recombinant adenoviruses in aerosolized fibrin glues through a multiluminal catheter could provide an optimal technique for gene transfer into epithelial cells in the mucosal surfece, which may have important implications for the treatment of human esophageal premalignant diseases.

AB - Background: Gene transfer to the esophageal epithelium holds the potential for the therapy of malignant as well as premalignant lesions in the upper gastrointestinal tract. Replication-deficient recombinant adenoviruses represent an efficient means of introducing genes in vivo into cells in a variety of organs. The majority of in vivo studies utilize direct submucosal injection for delivery of the viral vectors into the locoregional area of the gut; transferring genes into epithelial cells, however, is difficult because viruses are retained in the subepithelial space. To establish the efficient method for gene transfer into the epithelial cells, we have developed a multiluminal spray catheter that can be passed through the accessory channel of an endoscope, and we have evaluated the feasibility of fibrin glues as a vehicle of recombinant adenoviruses in a porcine model. Methods: The fibrinogen solution and the thrombion solution containing an E1/E3 deleted recombinant adenovirus expressing the bacterial lacZ gene (Ad-lacZ) were endoscopically sprayed on the porcine esophagus through the catheter attached to the dual-barrel syringe. Twenty-four hours after gene delivery, β -galactosidase activity of the esophagus was determined under the microscope following X-gal staining. Results: The fibrin glue could be locally sprayed on the porcine esophagus by using the multichannel catheter through the endoscope. Attachment of the fibrin glue comtining Ad-lacZ caused strong β-galactosidase staining on epithelial cells in the mucosal surface, but not in the basal cell layer. Conclusion: Endoscopic local delivery of recombinant adenoviruses in aerosolized fibrin glues through a multiluminal catheter could provide an optimal technique for gene transfer into epithelial cells in the mucosal surfece, which may have important implications for the treatment of human esophageal premalignant diseases.

KW - Adenovirus vector

KW - Esophageal epithelium

KW - Fibrin glue

KW - Gene delivery

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