Adenovirus-mediated gene transfer during initial organogenesis in the mammalian embryo is promoter-dependent and tissue-specific.
Replication-defective adenoviruses have received increasing attention as vectors for exogenous gene administration in a variety of experimental and pathological conditions. However, little information exists about their utility for in utero gene therapy, and no information exists concerning their efficacy for gene delivery during initial organogenesis in the mammalian embryo. To evaluate the feasibility of using these vectors for exogenous gene transduction during the initial stages of organogenesis in the mammal, we injected an adenovirus vector carrying the bacterial beta-galactosidase (lacZ) gene under the control of either the cytomegalovirus (CMV) promoter or the Rous sarcoma virus (RSV) long terminal repeat (LTR) into early, post-gastrulation, mouse embryos, and evaluated expression following 36-48 h in culture. These studies suggest that adenovirus-mediated gene delivery may provide an efficient method of gene transduction during critical developmental stages with no detectable adverse effects on normal development during early morphogenesis. In addition, the type of promoter used had a significant effect on the tissue distribution of gene expression.
Baldwin
H S
HS
Division of Pediatric Cardiology, Children's Hospital of Philadelphia, PA 19104, USA.
Mickanin
C
C
Buck
C
C
D000256:Adenoviridae; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics; D004622:Embryo, Mammalian; D004699:Endocardium / Q000196:embryology; D004730:Endothelium, Vascular / Q000196:embryology; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007763:Lac Operon; D051379:Mice; D008813:Mice, Inbred ICR; D009024:Morphogenesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid