Abstract
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 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 (Fig 1).

 

Figure 1: Long-term serial detection of LV-mediated firefly luciferase expression by bioluminescence imaging after injection of the fetal rat. The control animal was injected with normal saline solution; the other animals were injected with an LV encoding firefly luciferase in the lung, liver, and peritoneally. There is a significant signal at all time points in the experimental rats, whereas there is no signal above background in the control rat. Please note that the scales of the BLI images are different between the time points. (Reprinted from Toelen J, Deroose CM, Gijsbers R, et al. Fetal gene transfer with lentiviral vectors: long-term in vivo follow-up evaluation in a rat model. Am J Obstet Gynecol. 2007;196:352.e1-352.e6, with permission from Elsevier.)