Alveolar stem cell transduction by an adeno-associated viral vector

P. L. Zeitlin, S. Chu, C. Conrad, U. McVeigh, K. Ferguson, T. R. Flotte, W. B. Guggino

Research output: Contribution to journalArticlepeer-review

Abstract

In inherited disorders such as surfactant protein deficiencies or cystic fibrosis (CF), where lung damage develops progressively after birth, gene replacement is best accomplished in the neonatal period. We use the adeno-associated virus (AAV) as a vector for gene transfer in the newborn rabbit lung where stem cells are activated for lung growth and differentiation. AAV-mediated gene transfer as assayed by lacZ gene expression occurred preferentially in alveoli in the alveolar epithelial progenitor cell, the type II cell, and in the large airway tracheobronchial based and ciliated cells. Cell proliferation was confirmed by 5-bromo-deoxyuridine (BRDU) labeling in regions undergoing alveolarization and airway branch points. Regions of cell proliferation coincided with areas of significant lacZ expression. Thus, dividing and differentiating cells can be targeted by AAVlacZ delivery to newborn lung.

Original languageEnglish (US)
Pages (from-to)623-631
Number of pages9
JournalGene Therapy
Volume2
Issue number9
StatePublished - 1995

Keywords

  • Clara cell
  • alveolar Type II cell
  • basal cell
  • ciliated tracheal epithelial cell
  • cystic fibrosis
  • lacZ

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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