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  • Original Article - Enabling Technologies
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Original Article – Enabling Technologies

Chimeric rabies SADB19-VSVg-pseudotyped lentiviral vectors mediate long-range retrograde transduction from the mouse spinal cord

Gene Therapy volume 22, pages 357–364 (2015)Cite this article

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Abstract

Lentiviral vectors have proved an effective method to deliver transgenes into the brain; however, they are often hampered by a lack of spread from the site of injection. Modifying the viral envelope with a portion of a rabies envelope glycoprotein can enhance spread in the brain by using long-range axon projections to facilitate retrograde transport. In this study, we generated two chimeric envelopes containing the extra-virion and transmembrane domain of rabies SADB19 or CVS-N2c with the intra-virion domain of vesicular stomatitis virus. Viral particles were packaged containing a green fluorescent protein reporter construct under the control of the phosphoglycerokinase promoter. Both vectors produced high-titer particles with successful integration of the glycoproteins into the particle envelope and significant transduction of neurons in vitro. Injection of the SADB19 chimeric viral vector into the lumbar spinal cord of adult mice mediated a strong preference for gene transfer to local neurons and axonal terminals, with retrograde transport to neurons in the brainstem, hypothalamus and cerebral cortex. Development of this vector provides a useful means to reliably target select populations of neurons by retrograde targeting.

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Acknowledgements

We thank John Schofield, University of Otago for assistance in developing spinal cord surgeries and Louise Parr-Brownlie and Colin Brown for helpful discussions on the anatomical localization of transduced cells. This study was supported by a grant from the Royal Society of New Zealand Marsden Fund.

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Authors and Affiliations

  1. Department of Biochemistry, University of Otago, Dunedin, New Zealand

    L Schoderboeck, S Riad, A M Bokor, H E Wicky & S M Hughes

  2. Brain Health Research Centre, University of Otago, Dunedin, New Zealand

    L Schoderboeck, H E Wicky, M J Oswald, R M Empson & S M Hughes

  3. Otago Centre for Electron Microscopy, University of Otago, Dunedin, New Zealand

    M Strauss & M Bostina

  4. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA

    M Strauss

  5. Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand

    M Bostina

  6. Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand

    M J Oswald & R M Empson

  7. Genetics Otago, University of Otago, Dunedin, New Zealand

    S M Hughes

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  1. L Schoderboeck
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  2. S Riad
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  7. M J Oswald
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  9. S M Hughes
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Correspondence to S M Hughes.

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Schoderboeck, L., Riad, S., Bokor, A. et al. Chimeric rabies SADB19-VSVg-pseudotyped lentiviral vectors mediate long-range retrograde transduction from the mouse spinal cord. Gene Ther 22, 357–364 (2015). https://doi.org/10.1038/gt.2015.3

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