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Long-term transgene expression by administration of a lentivirus-based vector to the fetal circulation of immuno-competent mice

Gene Therapy volume 10, pages 1234–1240 (2003)Cite this article

Abstract

Inefficient gene transfer, inaccessibility of stem cell compartments, transient gene expression, and adverse immune and inflammatory reactions to vector and transgenic protein are major barriers to successful in vivo application of gene therapy for most genetic diseases. Prenatal gene therapy with integrating vectors may overcome these problems and prevent early irreparable organ damage. To this end, high-dose attenuated VSV-G pseudotyped equine infectious anaemia virus (EIAV) encoding β-galactosidase under the CMV promoter was injected into the fetal circulation of immuno-competent MF1 mice. We saw prolonged, extensive gene expression in the liver, heart, brain and muscle, and to a lesser extent in the kidney and lung of postnatal mice. Progressive clustered hepatocyte staining suggests clonal expansion of cells stably transduced. We thus provide proof of principle for efficient gene delivery and persistent transgene expression after prenatal application of the EIAV vector and its potential for permanent correction of genetic diseases.

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Acknowledgements

This work was sponsored by an MRC-programme Grant. S. Wadlington is funded by the Katherine Dormand Haemophilia Trust.

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Authors and Affiliations

  1. Division of Biomedical Sciences, Gene Therapy Research Group, Imperial College of Science Technology and Medicine, London, UK

    S N Waddington, S M K Buckley, M Nivsarkar, L Lawrence, F Al-Allaf, B Bigger, C Coutelle & M Themis

  2. Oxford BioMedica (UK), Oxford, UK

    K A Mitrophanous, F M Ellard, H T Cook & S M Kingsman

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  1. S N Waddington
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  2. K A Mitrophanous
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  3. F M Ellard
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Waddington, S., Mitrophanous, K., Ellard, F. et al. Long-term transgene expression by administration of a lentivirus-based vector to the fetal circulation of immuno-competent mice. Gene Ther 10, 1234–1240 (2003). https://doi.org/10.1038/sj.gt.3301991

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  • DOI: https://doi.org/10.1038/sj.gt.3301991

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