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Journal of Virology, July 2004, p. 6808-6817, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.6808-6817.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Transduction Profiles of Recombinant Adeno-Associated Virus Vectors Derived from Serotypes 2 and 5 in the Nigrostriatal System of Rats

Jean-Charles Paterna,^1* Joram Feldon,² and Hansruedi Büeler¹

Institute of Molecular Biology, University of Zurich, 8057 Zurich,¹ Laboratory of Behavioural Neurobiology, ETH Zurich, 8603 Schwerzenbach, Switzerland²

Received 10 October 2003/ Accepted 1 March 2004

We compared the transduction efficiencies and tropisms of titer-matched recombinant adeno-associated viruses (rAAV) derived from serotypes 2 and 5 (rAAV-2 and rAAV-5, respectively) within the rat nigrostriatal system. The two serotypes (expressing enhanced green fluorescent protein [EGFP]) were delivered by stereotaxic surgery into the same animals but different hemispheres of the striatum (STR), the substantia nigra (SN), or the medial forebrain bundle (MFB). While both serotypes transduced neurons effectively within the STR, rAAV-5 resulted in a much larger EGFP-expressing area than did rAAV-2. However, neurons transduced with rAAV-2 vectors expressed higher levels of EGFP. Consistent with this result, EGFP-positive projections emanating from transduced striatal neurons covered a larger area of the SN pars reticulata (SNr) after striatal delivery of rAAV-5, but EGFP levels in fibers of the SNr were higher after striatal injection of rAAV-2. We also compared the potentials of the two vectors for retrograde transduction and found that striatal delivery of rAAV-5 resulted in significantly more transduced dopaminergic cell bodies within the SN pars compacta and ventral tegmental area. Similarly, EGFP-transduced striatal neurons were detected only after nigral delivery of rAAV-5. Furthermore, we demonstrate that after striatal AAV-5 vector delivery, the transduction profiles were stable for as long as 9 months. Finally, although we did not target the hippocampus directly, efficient and widespread transduction of hippocampal neurons was observed after delivery of rAAV-5, but not rAAV-2, into the MFB.

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* Corresponding author. Mailing address: Institute of Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Phone: 41-1-635-3180. Fax: 41-1-635-6811. E-mail: smart{at}molbio.unizh.ch.

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Journal of Virology, July 2004, p. 6808-6817, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.6808-6817.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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