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. STUDY DESIGN: 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. CONCLUSION: 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, J; Deroose, CM; Gijsbers, R; Reumers, V; Sbragia, LN; Vets, S; Chitneni, SK; Bormans, G; Mortelmans, L; Deprest, JA; Debyser, Z
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