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Absence of an intrathecal immune reaction to a helper-dependent adenoviral vector delivered into the cerebrospinal fluid of non-human primates

Gene Therapy volume 15, pages 233–238 (2008)Cite this article

Abstract

Inflammation and immune reaction, or pre-existing immunity towards commonly used viral vectors for gene therapy severely impair long-term gene expression in the central nervous system (CNS), impeding the possibility to repeat the therapeutic intervention. Here, we show that injection of a helper-dependent adenoviral (HD-Ad) vector by lumbar puncture into the cerebrospinal fluid (CSF) of non-human primates allows long-term (three months) infection of neuroepithelial cells, also in monkeys bearing a pre-existing anti-adenoviral immunity. Intrathecal injection of the HD-Ad vector was not associated with any sign of systemic or local toxicity, nor by signs of a CNS-specific immune reaction towards the HD-Ad vector. Injection of HD-Ad vectors into the CSF circulation may thus represent a valuable approach for CNS gene therapy allowing for long-term expression and re-administration.

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Acknowledgements

This work was supported by grants from the Italian Multiple Sclerosis Foundation (FISM), the Myelin Project, the Cariplo Foundation and the Italian Ministry of Education and Scientific Research (MIUR-FIRB). We thank P Moullier and M Coville from the Animal Science Department of the Boisbonne Center, Nantes, for technical help and fruitful discussion.

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Authors and Affiliations

  1. Neuroimmunology Unit, San Raffaele Scientific Institute, Milan, Italy

    E Butti, A Bergami, E Brambilla, A Cattalini, G Martino & R Furlan

  2. Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy

    A Recchia & F Mavilio

  3. Laboratory of Neuroimmunology, C Mondino Neurological Institute, Pavia, Italy

    D Franciotta

  4. Molmed s.p.a., Milano, Italy

    A Stornaiuolo

  5. UMR 546, BEA de l'INSERM, Paris, France

    F Lachapelle

  6. Department of Neurological, San Raffaele Scientific Institute, Milan, Italy

    G Comi, G Martino & R Furlan

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  1. E Butti
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  2. A Bergami
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  3. A Recchia
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  9. G Comi
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  10. F Mavilio
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  11. G Martino
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  12. R Furlan
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Correspondence to R Furlan.

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Butti, E., Bergami, A., Recchia, A. et al. Absence of an intrathecal immune reaction to a helper-dependent adenoviral vector delivered into the cerebrospinal fluid of non-human primates. Gene Ther 15, 233–238 (2008). https://doi.org/10.1038/sj.gt.3303050

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  • DOI: https://doi.org/10.1038/sj.gt.3303050

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