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Efficient transduction of neurons using Ross River glycoprotein-pseudotyped lentiviral vectors

Gene Therapy volume 13, pages 966–973 (2006)Cite this article

Abstract

Lentiviral vectors are promising tools for CNS gene transfer since they efficiently transduce the cells of the nervous system in vivo. In this study, we have investigated the transduction efficiency of lentiviral vectors pseudotyped with Ross River virus glycoprotein (RRV-G) (RRV-G-pseudotyped lentiviral vectors (RRV-LV)). The RRV is an alphavirus with an extremely broad host range, including the cells of the central nervous system. Previous studies have shown that lentiviral vectors can be efficiently pseudotyped with this envelope protein and have demonstrated promising features of such vectors, including the possibility to establish stable producer cell lines. After injection of RRV-LV expressing green fluorescent protein into different structures in the rat brain we found efficient transduction of both neurons and glial cells. By using two cell-type-specific promoters, neuron-specific enolase and human glial fibrillary acidic protein, we demonstrated cell-specific transgene expression in the desired cell type. Ross River virus glycoprotein-pseudotyped lentiviral vectors also transduced human neural progenitor cells in vitro, showing that receptors for the RRV-G are present on human neural cells.

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Acknowledgements

We would in particular thank David A Sanders for providing the RRV-G envelope. Thanks also to Richard Kuhn for providing the anti-RRV E1 antibody and Didier Trono for providing the lentiviral vector system. Thanks to Bengt Mattsson, Ruben Smith, Anna-Karin Oldén, Ulla Jarl, Birgit Haraldson, Christina Isakson and Anneli Josefsson for technical assistance. This study was supported by the Swedish Research Council, Grant no. 13479.

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  1. Department of Experimental Medical Research, Section for Neuroscience, Wallenberg Neuroscience Center, Lund University, Lund, Sweden

    J Jakobsson, T Tolstrup Nielsen, K Staflin, B Georgievska & C Lundberg

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  1. J Jakobsson
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  2. T Tolstrup Nielsen
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  3. K Staflin
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  4. B Georgievska
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  5. C Lundberg
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Correspondence to C Lundberg.

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Jakobsson, J., Nielsen, T., Staflin, K. et al. Efficient transduction of neurons using Ross River glycoprotein-pseudotyped lentiviral vectors. Gene Ther 13, 966–973 (2006). https://doi.org/10.1038/sj.gt.3302701

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