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 beta-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.
journal_name
Gene Therjournal_title
Gene therapyauthors
Pitt BR,Schwarz MA,Pilewski JM,Nakayama D,Mueller GM,Robbins PD,Watkins SA,Albertine KH,Bland RDsubject
Has Abstractpub_date
1995-07-01 00:00:00pages
344-50issue
5eissn
0969-7128issn
1476-5462journal_volume
2pub_type
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