Gene transfer in utero biologically engineers a patent ductus arteriosus in lambs by arresting fibronectin-dependent neointimal formation

Catherine A.E. Mason, Jean Luc Bigras, Stacy B. O'Blenes, Bin Zhou, Brendan McIntyre, Norimasa Nakamura, Yasufumi Kaneda, Marlene Rabinovitch

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Closure of the ductus arteriosus requires prenatal formation of intimal cushions, which occlude the vessel lumen at birth. Survival of newborns with severe congenital heart defects, however, depends on ductal patency. We used a gene transfer approach to create a patent ductus arteriosus by targeting the fibronectin-dependent smooth muscle cell migration required for intimal cushion formation. Fetal lamb ductus arteriosus was transfected in utero with hemagglutinating virus of Japan liposomes containing plasmid encoding 'decoy' RNA to sequester the fibronectin mRNA binding protein. Fibronectin translation was inhibited and intimal cushion formation was prevented. We thus established the essential role of fibronectin-dependent smooth muscle cell migration in intimal cushion formation in the intact animal and the feasibility of incorporating biological engineering in the management of congenital heart disease.

Original languageEnglish (US)
Pages (from-to)176-182
Number of pages7
JournalNature Medicine
Volume5
Issue number2
DOIs
StatePublished - Feb 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Mason, C. A. E., Bigras, J. L., O'Blenes, S. B., Zhou, B., McIntyre, B., Nakamura, N., Kaneda, Y., & Rabinovitch, M. (1999). Gene transfer in utero biologically engineers a patent ductus arteriosus in lambs by arresting fibronectin-dependent neointimal formation. Nature Medicine, 5(2), 176-182. https://doi.org/10.1038/5538