Direct in vivo adenovirus-mediated gene transfer to salivary glands

A. Mastrangeli, B. O'Connell, W. Aladib, P. C. Fox, B. J. Baum, Ronald Crystal

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Abstract

Gene transfer to the salivary glands holds the potential for the therapy of salivary gland disorders and for delivery of therapeutic proteins to the mouth and upper gastrointestinal tract. Administration of the recombinant adenovirus vectors Ad.RSVβgal [coding for the intracellular protein β- galactosidase (β-Gal)] and Adα1AT [coding for human α1-antitrypsin (α1- AT), a secreted protein] to salivary gland cell lines in vitro demonstrated exogenous gene expression. Retrograde ductal injection of the Ad.RSVβgal vector to rat salivary glands in vivo resulted in β-Gal expression in acinar and ductal cells. Exposure of submandibular glands in vivo to Adα1AT resulted in expression of α1-AT mRNA transcripts, de novo synthesis of α1-AT, and secretion in the saliva. To evaluate the feasibility of adenovirus-mediated gene transfer to human glands, human minor salivary glands were infected ex vivo with Ad.RSVβgal, and implanted into severe combined immunodeficient mice. Evaluation of the human tissue demonstrated β-Gal activity. These observations demonstrate that adenovirus vectors are capable of direct delivery of genes to the salivary glands, suggesting a variety of possible gene therapy applications.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume266
Issue number6 29-6
Publication statusPublished - 20 Jul 1994
Externally publishedYes

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Keywords

  • α-antitrypsin
  • β-galactosidase
  • exocrine glands

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

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