Fetal gene transfer with lentiviral vectors: long-term in vivo follow-up evaluation in a rat model

被引:13
|
作者
Toelen, Jaan [1 ]
Deroose, Christophe M. [1 ]
Gijsbers, Rik [1 ]
Reumers, Veerle [1 ]
Sbragia, Lourenco N. [1 ]
Vets, Sofie [1 ]
Chitneni, Satish K. [1 ]
Bormans, Guy [1 ]
Mortelmans, Luc [1 ]
Deprest, Jan A. [1 ]
Debyser, Zeger [1 ]
机构
[1] Katholieke Univ Leuven, Fac Med, Ctr Surg Technol, B-3000 Louvain, Belgium
关键词
fetal intervention; gene therapy; lentiviral vector; noninvasive imaging;
D O I
10.1016/j.ajog.2007.01.038
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
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.
引用
收藏
页码:352.e1 / 352.e6
页数:6
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