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

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 beta-galactosidase reporter gene (AdRSVbetagal) 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 beta-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 beta-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.

journal_name

Am J Obstet Gynecol

journal_title

American journal of obstetrics and gynecology

authors

Weisz B,David AL,Gregory LG,Perocheau D,Ruthe A,Waddington SN,Themis M,Cook T,Coutelle C,Rodeck CH,Peebles DM

doi

10.1016/j.ajog.2005.06.077

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

1105-9

issue

3 Pt 2

eissn

0002-9378

issn

1097-6868

pii

S0002-9378(05)00980-4

journal_volume

193

pub_type

杂志文章

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