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

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.

Kornum BR ，Stott SR ，Mattsson B ，Wisman L ，Ettrup A ，Hermening S ，Knudsen GM ，Kirik D ... -  《-》

Targeted in utero delivery of a retroviral vector for gene transfer in the rodent brain.

Stott SR ，Kirik D 《-》

[Gene transfer efficiencies and cell tropism of recombinant adeno-associated virus in the hippocampus of adult rat].

L i SF ，Li ZJ ，Li GL ，Dou WC ，Zhang ZX ，Wei JJ ，Kong YG ，Xu L ，Gao J ，Wang RZ ... -  《-》

Transduction profiles of recombinant adeno-associated virus vectors derived from serotypes 2 and 5 in the nigrostriatal system of rats.

Paterna JC ，Feldon J ，Büeler H 《-》

Preferential expression of an AAV-2 construct in NOS-positive interneurons following intrastriatal injection.

Sin M ，Walker PD ，Bouhamdan M ，Quinn JP ，Bannon MJ ... -  《-》