Fetal gene transfer with lentiviral vectors: long-term in vivo follow-up evaluation in a rat model.
OBJECTIVE
The purpose of this study was to evaluate the long-term expression of a transgene and subsequent immune response after the injection of lentiviral vectors in a fetal rats.


METHODS
Fetal rats were injected in the liver, peritoneal cavity, or lung at E19 (term, E21) with a lentiviral vector expressing enhanced green fluorescent protein and luciferase. Controls received saline solution. After birth, full body bioluminescence was done at weeks 1, 4, 10, and 30 of life; seroconversion for the transgene was assessed.


RESULTS
All surviving fetuses that had been injected in the liver (8/9 fetuses), peritoneum (3/3 fetuses), or lung (9/10 fetuses) showed a signal on bioluminescence imaging scan up to 30 weeks. None of the survivors displayed seroconversion against the transgene.


CONCLUSIONS
In the rat model, the administration of lentiviral vectors into the fetal lung and liver resulted in long-term transgene expression without detectable humoral immune response.
Toelen
Jaan
J
Department of Pediatrics, University Hospital Gasthuisberg, Belgium.
Deroose
Christophe M
CM
Gijsbers
Rik
R
Reumers
Veerle
V
Sbragia
Lourenço N
LN
Vets
Sofie
S
Chitneni
Satish K
SK
Bormans
Guy
G
Mortelmans
Luc
L
Deprest
Jan A
JA
Debyser
Zeger
Z
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000276:immunology / Q000473:pathology; D005500:Follow-Up Studies; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000494:pharmacology*; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics*; D008099:Liver / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D049268:Positron-Emission Tomography; D011247:Pregnancy; D011270:Pregnancy, Animal; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D013997:Time Factors; D014161:Transduction, Genetic