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Gene Transfer to the Cerebellum

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Abstract

There are several diseases for which gene transfer therapy to the cerebellum might be practicable. In these studies, we used recombinant Tag-deleted SV40-derived vectors (rSV40s) to study gene delivery targeting the cerebellum. These vectors transduce neurons and microglia very effectively in vitro and in vivo, and so we tested them to evaluate gene transfer to the cerebellum in vivo. Using a rSV40 vector carrying human immunodeficiency virus (HIV)-Nef with a C-terminal FLAG epitope, we characterized the distribution, duration, and cell types transduced. Rats received test and control vectors by stereotaxic injection into the cerebellum. Transgene expression was assessed 1, 2, and 4 weeks later by immunostaining of serial brain sections. FLAG epitope-expressing cells were seen, at all times after vector administration, principally detected in the Purkinje cells of the cerebellum, identified as immunopositive for calbindin. Occasional microglial cells were tranduced; transgene expression was not detected in astrocytes or oligodendrocytes. No inflammatory or other reaction was detected at any time. Thus, SV40-derived vectors can deliver effective, safe, and durable transgene expression to the cerebellum.

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Acknowledgments

This work was supported by the National Institutes of Health (NIH) grant MH70287.

Conflicts of interest

The authors of this manuscript have no potential conflict of interest in the submission. The manuscript has not been published before and is not under consideration anywhere else. The publication has been approved by all co-authors.

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Authors and Affiliations

  1. Department of Pathology, Jefferson Medical College, Thomas Jefferson University, 1020 Locust Street, Room 255, Philadelphia, PA, 19107, USA

    Jean-Pierre Louboutin & David S. Strayer

  2. Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Beverly A. S. Reyes & Elisabeth J. Van Bockstaele

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  1. Jean-Pierre Louboutin
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  2. Beverly A. S. Reyes
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Correspondence to Jean-Pierre Louboutin.

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Louboutin, JP., Reyes, B.A.S., Van Bockstaele, E.J. et al. Gene Transfer to the Cerebellum. Cerebellum 9, 587–597 (2010). https://doi.org/10.1007/s12311-010-0202-9

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