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Efficient CNS gene delivery by intravenous injection

Abstract

We administered recombinant SV40-derived viral vectors (rSV40s) intravenously to mice with or without prior intraperitoneal injection of mannitol to deliver transgenes to the central nervous system (CNS). We detected transgene-expressing cells (mainly neurons) most prominently in the cortex and spinal cord; prior intraperitoneal mannitol injection increased CNS gene delivery tenfold. Intravenous injection of rSV40s, particularly with mannitol pretreatment, resulted in extensive expression of multiple transgenes throughout the CNS.

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Figure 1: AU1 expression from a transgene after intravenous injection of recombinant SV40 virus.
Figure 2: Transgene-expressing cells were mostly neurons.
Figure 3: Distribution of AU1 expression in the brain.
Figure 4: Expression of transgene-encoded AU1 in the spinal cord.

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Acknowledgements

We thank J. Altemus for technical help. Funding was provided by the US National Institutes of Health (MH70287, MH69122 and AI48244 to D.S.S., DK68216 to J.R.C.).

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Authors and Affiliations

Authors

Contributions

J.-P.L. designed and performed experiments, processed and analyzed data, and wrote the paper. A.A.C. performed experiments and designed vectors. E.M. designed vectors. J.R.C. analyzed data and provided collaboration and grant support. D.S.S. coordinated the project and helped to write the paper.

Corresponding author

Correspondence to Jean-Pierre Louboutin.

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The authors declare no competing financial interests.

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Louboutin, JP., Chekmasova, A., Marusich, E. et al. Efficient CNS gene delivery by intravenous injection. Nat Methods 7, 905–907 (2010). https://doi.org/10.1038/nmeth.1518

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