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• W2080967040 abstract "Gene transfer into neurons is a major goal for molecular genetic studies of the nervous system and for the development of gene therapies for several human neurological disorders. However, transduction efficiency in target cells is a major hurdle for gene delivery with a restricted region of transgene expression. With this respect, recombinant adeno-associated viruses (rAAV) are highly efficient for gene transfer to the central nervous system (CNS). Several different rAAV serotypes have been described for gene delivery to the CNS but there are few comparative studies evaluating their distribution in the adult mouse brain. The aim of this work was to evaluate the transduction efficiency of different rAAV serotypes (AAVs 1, 2, 5, 8 and chimeric 1/2 - 1/8) by convection enhanced delivery (CED) to the mouse striatum. The AAV vectors used in this study, AAV-CBA-GFP-W, carries AAV2 ITRs, a hybrid CMV enhancer/chicken beta-actin promoter (CBA) to control transgene expression, a WPRE element, and a BGH polyA signal. All different serotyped vectors were produced by triple transient transfection of 293T cells, and purified using a discontinuous iodixanol gradient followed by anion exchange chromatography. One |[mu]|l of each virus stock (titers normalized to 1.7|[times]|1013 g.c./ml) was infused stereotaxically into the left striatum (coordinates from bregma: AP +0.5 mm; ML +2.0 mm; DV |[minus]|2.5 mm) of 6-8 weeks old nude mice by convection-enhanced delivery (CED) at 0.1 |[mu]|l.min-1. One month later mice were sacrificed and the brain analyzed for GFP expression. Preliminary analysis for the individual serotypes indicates that AAVs 1 and 8 are the most efficient in transduction within the striatum. Furthermore, we could verify GFP expression in other structures. On the other hand, AAVs 2 and 5 had a more limited distribution in the mouse striatum. We have also analyzed two different combinations of AAV serotypes displaying chimeric capsids and verified that AAV 1/8 is the most efficient in GFP transduction. Interestingly, AAV1/8 positive staining was verified throughout most of the striatum and in structures like the hippocampus. These results suggest that AAV1 and 8 serotypes alone are very efficient in brain transduction and this effect may be amplified if they are combined in a chimeric form (AAV 1/8). In conclusion, the differences observed here might be taken into account to develop novel gene transfer strategies for neurologic diseases." @default.
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• W2080967040 title "866. Recombinant AAV 1, 2, 5, 8 and Chimeric 1/2-1/8 Serotypes Display Differential Transduction Efficiency after Delivery to Mouse Brain" @default.
• W2080967040 doi "https://doi.org/10.1016/j.ymthe.2005.07.409" @default.
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