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

Research output: Contribution to journalArticle

118 Citations (Scopus)

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

Fingerprint

Salivary Glands
Adenoviridae
Genes
Galactosidases
Salivary Proteins and Peptides
Minor Salivary Glands
Upper Gastrointestinal Tract
SCID Mice
Acinar Cells
Submandibular Gland
Saliva
Genetic Therapy
Mouth
Proteins
Gene Expression
Cell Line
Messenger RNA
Injections
Therapeutics

Keywords

  • α-antitrypsin
  • β-galactosidase
  • exocrine glands

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Direct in vivo adenovirus-mediated gene transfer to salivary glands. / Mastrangeli, A.; O'Connell, B.; Aladib, W.; Fox, P. C.; Baum, B. J.; Crystal, Ronald.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 266, No. 6 29-6, 20.07.1994.

Research output: Contribution to journalArticle

Mastrangeli, A. ; O'Connell, B. ; Aladib, W. ; Fox, P. C. ; Baum, B. J. ; Crystal, Ronald. / Direct in vivo adenovirus-mediated gene transfer to salivary glands. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 1994 ; Vol. 266, No. 6 29-6.
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