Retrovirus-mediated gene transfer in lungs of living fetal sheep

B. R. Pitt, M. A. Schwarz, J. M. Pilewski, D. Nakayama, G. M. Mueller, P. D. Robbins, S. A. Watkins, K. H. Albertine, R. D. Bland

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

In utero somatic gene transfer may be a useful therapeutic strategy for a variety of inherited disorders. In the present study, we demonstrate transgene expression in the airways of fetal lamb lungs, 2-3 weeks after injection of Moloney murine leukemia retrovirus based vectors containing cDNA for β-galactosidase (lacZ) or human interleukin receptor antagonist protein (IRAP), into the fluid filled future airspace of fully catheterized twin fetal lambs (104-117 days gestational age; term 147 days). Expression of lacZ or IRAP was limited to the twin that received the respective vector and was apparent, at light microscopic level, in the epithelium and submucosal space of proximal airways, and to a lesser extent, in the respiratory epithelium of the distal airways. These data demonstrate for the first time that transfer of foreign DNA to fetal lung can be accomplished. These findings support the use of retroviral vectors for somatic lung DNA transfer and suggest that inherited disorders such as cystic fibrosis may be approached therapeutically via gene transfer, in utero.

Original languageEnglish (US)
Pages (from-to)344-350
Number of pages7
JournalGene Therapy
Volume2
Issue number5
StatePublished - 1995

Keywords

  • epithelium
  • fetal
  • lung
  • retrovirus

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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