Percutaneous ultrasound-guided injection of the trachea in fetal sheep: a novel technique to target the fetal airways.
OBJECTIVE
To access the fetal airways percutaneously using ultrasound-guided injection of the fetal trachea in sheep.


METHODS
Adenoviral gene therapy vectors and transduction-enhancing agents were delivered to the trachea via a needle inserted through the thorax or the neck of late-gestation (0.9 term, n = 3) or mid-gestation (0.5-0.8 term, n = 18) fetal sheep using ultrasound guidance.


RESULTS
Injection of the trachea in the fetal thorax was successful in 16 out of 18 fetuses and achieved at the first attempt in 9 fetuses within 12 min [mean 7 min and 31 s +/- (SD) 3 min and 4 s]. Survival was 100%. Injecting the trachea in the neck was less successful.


CONCLUSIONS
The fetal trachea of the sheep can be safely accessed by percutaneous ultrasound-guided injection to deliver vectors directly to the fetal airways for gene therapy. It may also enable tracheal occlusion for the antenatal treatment of congenital diaphragmatic hernia without the need for endoscopy or open surgery.
David
A L
AL
Department of Obstetrics and Gynaecology, Royal Free and University College London Medical School, London, UK. a.david@ucl.ac.uk
Peebles
D M
DM
Gregory
L
L
Themis
M
M
Cook
T
T
Coutelle
C
C
Rodeck
C H
CH
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D003550:Cystic Fibrosis / Q000000981:diagnostic imaging / Q000628:therapy*; D005260:Female; D005315:Fetal Diseases / Q000000981:diagnostic imaging / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D007267:Injections / Q000379:methods; D009333:Neck / Q000000981:diagnostic imaging; D011247:Pregnancy; D012756:Sheep; D014132:Trachea / Q000000981:diagnostic imaging*; D016216:Ultrasonography, Prenatal