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This Article Full Text Full Text (PDF) All Versions of this Article: 90/1/53    most recent expphysiol.2004.028159v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shevtsova, Z. Articles by Kügler, S. Search for Related Content PubMed PubMed Citation Articles by Shevtsova, Z. Articles by Kügler, S. Related Collections Symposia Papers

¹ Department of Neurology, Vector Laboratory, University of Göttingen, Medical School, Waldweg 33, 37073, Göttingen, Germany

Abstract

The brain parenchyma consists of several different cell types, such as neurones, astrocytes, microglia, oligodendroglia and epithelial cells, which are morphologically and functionally intermingled in highly complex three-dimensional structures. These different cell types are also present in cultures of brain cells prepared to serve as model systems of CNS physiology. Gene transfer, either in a therapeutic attempt or in basic research, is a fascinating and promising tool to manipulate both the complex physiology of the brain and that of isolated neuronal cells. Viral vectors based on the parvovirus, adeno-associated virus (AAV), have emerged as powerful transgene delivery vehicles. Here we describe highly efficient targeting of AAV vectors to either neurones or astrocytes in cultured primary brain cell cultures. We also show that transcriptional targeting can be achieved by the use of small promoters, significantly boosting the transgene capacity of the recombinant viral genome. However, we also demonstrate that successful targeting of a vector in vitro does not necessarily imply that the same targeting works in the adult brain. Cross-packaging the AAV-2 genome in capsids of other serotypes adds additional benefits to this vector system. In the brain, the serotype-5 capsid allows for drastically increased spread of the recombinant vector as compared to the serotype-2 capsid. Finally, we emphasize the optimal targeting approach, in which the natural tropism of a vector for a specific cell type is employed. Taken together, these data demonstrate the flexibility which AAV-based vector systems offer in physiological research.

(Received 16 September 2004; accepted after revision 2 November 2004; first published online 12 November 2004)
Corresponding author S. Kügler: Department of Neurology, Vector Laboratory, Waldweg 33, 37073 Göttingen, Germany. Email: sebastian.kuegler{at}med.uni-goettingen.de

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