Targeting the respiratory muscles of fetal sheep for prenatal gene therapy for Duchenne muscular dystrophy

Boaz Weisz*, Anna L. David, Lisa G. Gregory, Dany Perocheau, Ali Ruthe, Simon N. Waddington, Mike Themis, Terry Cook, Charles Coutelle, Charles H. Rodeck, Donald M. Peebles

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Duchenne muscular dystrophy (DMD) is a lethal degenerative muscular disease. Fetal gene therapy may correct the primary genetic defect. Our aim was to achieve expression of a reporter gene in the respiratory muscles of early gestation fetal sheep. Study design: An adenovirus vector containing the β-galactosidase reporter gene (AdRSVβgal) was injected into the thoracic musculature (n = 3) and pleural cavity (n = 6) of fetal sheep (61-67 days' gestation) under ultrasound guidance. Tissues were harvested after 48 hours and site and intensity of β-galactosidase expression were assessed. Results: Limited transgene expression observed after a single injection was improved by multiple injections, but remained localized. Ultrasound-guided creation of a hydrothorax led to an increase in the intensity of β-galactosidase expression (ELISA). X-gal staining and immunohistochemistry showed that vector spread was confined to the innermost intercostal musculature. Conclusion: Ultrasound-guided injection can deliver gene therapy vectors to the fetal pleural cavity and achieve transduction of the respiratory muscles.

Original languageEnglish
Pages (from-to)1105-1109
Number of pages5
JournalAmerican Journal of Obstetrics and Gynecology
Volume193
Issue number3 SUPPL.
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • Duchenne muscular dystrophy
  • Fetal gene therapy
  • Fetal medicine
  • Gene therapy
  • Ultrasound

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