Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain

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Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain. / Kornum, Birgitte R; Stott, Simon R W; Mattsson, Bengt; Wisman, Liselijn; Ettrup, Anders; Hermening, Stephan; Knudsen, Gitte M; Kirik, Deniz.

In: Experimental Neurology, Vol. 222, No. 1, 01.03.2010, p. 70-85.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Kornum, BR, Stott, SRW, Mattsson, B, Wisman, L, Ettrup, A, Hermening, S, Knudsen, GM & Kirik, D 2010, 'Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain', Experimental Neurology, vol. 222, no. 1, pp. 70-85. https://doi.org/10.1016/j.expneurol.2009.12.009

APA

Kornum, B. R., Stott, S. R. W., Mattsson, B., Wisman, L., Ettrup, A., Hermening, S., ... Kirik, D. (2010). Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain. Experimental Neurology, 222(1), 70-85. https://doi.org/10.1016/j.expneurol.2009.12.009

Vancouver

Kornum BR, Stott SRW, Mattsson B, Wisman L, Ettrup A, Hermening S et al. Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain. Experimental Neurology. 2010 Mar 1;222(1):70-85. https://doi.org/10.1016/j.expneurol.2009.12.009

Author

Kornum, Birgitte R ; Stott, Simon R W ; Mattsson, Bengt ; Wisman, Liselijn ; Ettrup, Anders ; Hermening, Stephan ; Knudsen, Gitte M ; Kirik, Deniz. / Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain. In: Experimental Neurology. 2010 ; Vol. 222, No. 1. pp. 70-85.

Bibtex

@article{37d7b6d50cdf4ca483c5546516fcbbef,
title = "Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain",
abstract = "Viral vector-mediated gene transfer has emerged as a powerful means to target transgene expression in the central nervous system. Here we characterized the efficacy of serotypes 1 and 5 recombinant adeno-associated virus (rAAV) vectors encoding green fluorescent protein (GFP) after stereotaxic delivery to the neonatal rat and minipig striatum. The efficiency of GFP expression and the phenotype of GFP-positive cells were assessed within the forebrain at different time points up to 12 months after surgery. Both rAAV1-GFP and rAAV5-GFP delivery resulted in transduction of the striatum as well as striatal input and output areas, including large parts of the cortex. In both species, rAAV5 resulted in a more widespread transgene expression compared to rAAV1. In neonatal rats, rAAV5 also transduced several other areas such as the olfactory bulbs, hippocampus, and septum. Phenotypic analysis of the GFP-positive cells, performed using immunohistochemistry and confocal microscopy, showed that most of the GFP-positive cells by either serotype were NeuN-positive neuronal profiles. The rAAV5 vector further displayed the ability to transduce non-neuronal cell types in both rats and pigs, albeit at a low frequency. Our results show that striatal delivery of rAAV5 vectors in the neonatal brain represents a useful tool to express genes of interest both in the basal ganglia and the neocortex. Furthermore, we apply, for the first time, viral vector-mediated gene transfer to the pig brain providing the opportunity to study effects of genetic manipulation in this non-primate large animal species. Finally, we generated an atlas of the G{\"o}ttingen minipig brain for guiding future studies in this large animal species.",
author = "Kornum, {Birgitte R} and Stott, {Simon R W} and Bengt Mattsson and Liselijn Wisman and Anders Ettrup and Stephan Hermening and Knudsen, {Gitte M} and Deniz Kirik",
note = "Copyright 2009 Elsevier Inc. All rights reserved.",
year = "2010",
month = "3",
day = "1",
doi = "http://dx.doi.org/10.1016/j.expneurol.2009.12.009",
language = "English",
volume = "222",
pages = "70--85",
journal = "Experimental Neurology",
issn = "0014-4886",
publisher = "Academic Press",
number = "1",

}

RIS

TY - JOUR

T1 - Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain

AU - Kornum, Birgitte R

AU - Stott, Simon R W

AU - Mattsson, Bengt

AU - Wisman, Liselijn

AU - Ettrup, Anders

AU - Hermening, Stephan

AU - Knudsen, Gitte M

AU - Kirik, Deniz

N1 - Copyright 2009 Elsevier Inc. All rights reserved.

PY - 2010/3/1

Y1 - 2010/3/1

N2 - Viral vector-mediated gene transfer has emerged as a powerful means to target transgene expression in the central nervous system. Here we characterized the efficacy of serotypes 1 and 5 recombinant adeno-associated virus (rAAV) vectors encoding green fluorescent protein (GFP) after stereotaxic delivery to the neonatal rat and minipig striatum. The efficiency of GFP expression and the phenotype of GFP-positive cells were assessed within the forebrain at different time points up to 12 months after surgery. Both rAAV1-GFP and rAAV5-GFP delivery resulted in transduction of the striatum as well as striatal input and output areas, including large parts of the cortex. In both species, rAAV5 resulted in a more widespread transgene expression compared to rAAV1. In neonatal rats, rAAV5 also transduced several other areas such as the olfactory bulbs, hippocampus, and septum. Phenotypic analysis of the GFP-positive cells, performed using immunohistochemistry and confocal microscopy, showed that most of the GFP-positive cells by either serotype were NeuN-positive neuronal profiles. The rAAV5 vector further displayed the ability to transduce non-neuronal cell types in both rats and pigs, albeit at a low frequency. Our results show that striatal delivery of rAAV5 vectors in the neonatal brain represents a useful tool to express genes of interest both in the basal ganglia and the neocortex. Furthermore, we apply, for the first time, viral vector-mediated gene transfer to the pig brain providing the opportunity to study effects of genetic manipulation in this non-primate large animal species. Finally, we generated an atlas of the Göttingen minipig brain for guiding future studies in this large animal species.

AB - Viral vector-mediated gene transfer has emerged as a powerful means to target transgene expression in the central nervous system. Here we characterized the efficacy of serotypes 1 and 5 recombinant adeno-associated virus (rAAV) vectors encoding green fluorescent protein (GFP) after stereotaxic delivery to the neonatal rat and minipig striatum. The efficiency of GFP expression and the phenotype of GFP-positive cells were assessed within the forebrain at different time points up to 12 months after surgery. Both rAAV1-GFP and rAAV5-GFP delivery resulted in transduction of the striatum as well as striatal input and output areas, including large parts of the cortex. In both species, rAAV5 resulted in a more widespread transgene expression compared to rAAV1. In neonatal rats, rAAV5 also transduced several other areas such as the olfactory bulbs, hippocampus, and septum. Phenotypic analysis of the GFP-positive cells, performed using immunohistochemistry and confocal microscopy, showed that most of the GFP-positive cells by either serotype were NeuN-positive neuronal profiles. The rAAV5 vector further displayed the ability to transduce non-neuronal cell types in both rats and pigs, albeit at a low frequency. Our results show that striatal delivery of rAAV5 vectors in the neonatal brain represents a useful tool to express genes of interest both in the basal ganglia and the neocortex. Furthermore, we apply, for the first time, viral vector-mediated gene transfer to the pig brain providing the opportunity to study effects of genetic manipulation in this non-primate large animal species. Finally, we generated an atlas of the Göttingen minipig brain for guiding future studies in this large animal species.

U2 - http://dx.doi.org/10.1016/j.expneurol.2009.12.009

DO - http://dx.doi.org/10.1016/j.expneurol.2009.12.009

M3 - Journal article

VL - 222

SP - 70

EP - 85

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - 1

ER -

ID: 34143038