Adenovirus-mediated transfer of human lipase complementary DNA to the gallbladder

Hiroyuki Maeda, Claire Danel, Ronald Crystal

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Background/Aims: Despite many improvements in current therapy, exocrine pancreatic insufficiency remains a significant problem in cystic fibrosis. To establish a new therapy for exocrine pancreatic insufficiency, the feasibility of transferring the human pancreatic lipase complementary DNA to the gallbladder as a possible target using a recombinant adenovirus vector was evaluated. Methods: The adenovirus vector AdCMV.Lip was constructed using the cytomegalovirus immediate early promoter to drive the human pancreatic lipase complementary DNA. In vitro infection of the human gallbladder epithelial cell line HS-181 and ex vivo infection of the sheep gallbladder with AdRSV.β-gal (an adenovirus vector containing the Escherichia coli lacZ [(β-galactosidase] gene) or AdCMV.Lip were evaluated. Results: The supernatant from AdCMV.Lip-infected HS-181 showed the secretion of active lipase for at least 2 weeks in vitro. The epithelium of gallbladder infected with AdRSV.β-gal ex vivo showed the expression of the β galactosidase. The fluid from the gallbladder lumen infected with AdCMV.Lip showed the increased lipase activity.Conclusions: These observations show that an adenovirus vector can transfer a human pancreatic enzyme in vitro and ex vivo, suggesting the feasibility of in vivo gene therapy for exocrine pancreatic insufficiency in cystic fibrosis.

Original languageEnglish
Pages (from-to)1638-1644
Number of pages7
JournalGastroenterology
Volume106
Issue number6
DOIs
Publication statusPublished - 1 Jan 1994
Externally publishedYes

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Gallbladder
Lipase
Adenoviridae
Lip
Exocrine Pancreatic Insufficiency
Complementary DNA
Galactosidases
Cystic Fibrosis
Lac Operon
Infection
Cytomegalovirus
Genetic Therapy
Sheep
Epithelium
Epithelial Cells
Escherichia coli
Cell Line
Enzymes
Therapeutics
In Vitro Techniques

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Adenovirus-mediated transfer of human lipase complementary DNA to the gallbladder. / Maeda, Hiroyuki; Danel, Claire; Crystal, Ronald.

In: Gastroenterology, Vol. 106, No. 6, 01.01.1994, p. 1638-1644.

Research output: Contribution to journalArticle

Maeda, Hiroyuki ; Danel, Claire ; Crystal, Ronald. / Adenovirus-mediated transfer of human lipase complementary DNA to the gallbladder. In: Gastroenterology. 1994 ; Vol. 106, No. 6. pp. 1638-1644.
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