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Intracisternal rSV40 administration provides effective pan-CNS transgene expression

Gene Therapy volume 19, pages 114–118 (2012)Cite this article

Abstract

Potential genetic treatments for many generalized central nervous system (CNS) diseases require transgene expression throughout the CNS. Using oxidant stress and apoptosis caused by HIV-1 envelope gp120 as a model, we studied pan-CNS neuroprotective gene delivery into the cisterna magna (CM). Recombinant SV40 vectors carrying Cu/Zn superoxide dismutase or glutathione peroxidase were injected into rat CMs following intraperitoneal administration of mannitol. Sustained transgene expression was seen in neurons throughout the CNS. On challenge, 8 weeks later with gp120 injected into the caudate putamen, significant neuroprotection was documented. Thus, intracisternal administration of antioxidant-carrying rSV40 vectors may be useful in treating widespread CNS diseases such as HIV-1-associated neurocognitive disorders characterized by oxidative stress.

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Acknowledgements

This work was supported by NIH grants MH69122 and MH70287.

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Authors and Affiliations

  1. Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA

    J-P Louboutin, L Agrawal & D S Strayer

  2. Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA, USA

    B A S Reyes & E J Van Bockstaele

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  1. J-P Louboutin
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  2. B A S Reyes
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  3. L Agrawal
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  4. E J Van Bockstaele
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  5. D S Strayer
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Correspondence to J-P Louboutin.

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Louboutin, JP., Reyes, B., Agrawal, L. et al. Intracisternal rSV40 administration provides effective pan-CNS transgene expression. Gene Ther 19, 114–118 (2012). https://doi.org/10.1038/gt.2011.75

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