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

Am J Obstet Gynecol. 2007 Apr;196(4):352.e1-6. doi: 10.1016/j.ajog.2007.01.038.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Fetus / immunology
  • Fetus / pathology
  • Follow-Up Studies
  • Gene Transfer Techniques
  • Genetic Therapy / methods
  • Genetic Vectors / pharmacology*
  • Immunohistochemistry
  • Lentivirus / genetics*
  • Liver / immunology
  • Liver / pathology
  • Lung / immunology
  • Lung / pathology
  • Positron-Emission Tomography
  • Pregnancy
  • Pregnancy, Animal*
  • Probability
  • Rats
  • Rats, Wistar
  • Reference Values
  • Sensitivity and Specificity
  • Time Factors
  • Transduction, Genetic*