Promoters and serotypes: targeting of adeno-associated virus vectors for gene transfer in the rat central nervous system in vitro and in vivo

2005 | conference paper; research paper. A publication with affiliation to the University of Göttingen.

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​Promoters and serotypes: targeting of adeno-associated virus vectors for gene transfer in the rat central nervous system in vitro and in vivo​
Shevtsova, Z.; Malik, J. M. I.; Michel, U. ; Bähr, M.   & Kugler, S. ​ (2005)
​Experimental Physiology (1) pp. 53​-59. (Vol. 90). ​Meeting on Viral Gene Transfer in Neuroscience​, Univ Bristol, Bristol, ENGLAND.
Oxford​: Blackwell Publishing Ltd. DOI: https://doi.org/10.1113/expphysiol.2004.028159 

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Authors
Shevtsova, Zinayida; Malik, J. M. I.; Michel, Uwe ; Bähr, Mathias ; Kugler, S. 
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 recombinantviral 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.
Issue Date
2005
Publisher
Blackwell Publishing Ltd
Conference
Meeting on Viral Gene Transfer in Neuroscience
Conference Place
Univ Bristol, Bristol, ENGLAND
ISSN
0958-0670

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