Analysis of Transduction Efficiency, Tropism and Axonal Transport of AAV Serotypes 1, 2, 5, 6, 8 and 9 in the Mouse Brain
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Open Access
- 27 September 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (9), e76310
- https://doi.org/10.1371/journal.pone.0076310
Abstract
Recombinant Adeno-associated virus vectors (rAAV) are widely used for gene delivery and multiple naturally occurring serotypes have been harnessed to target cells in different tissues and organs including the brain. Here, we provide a detailed and quantitative analysis of the transduction profiles of rAAV vectors based on six of the most commonly used serotypes (AAV1, AAV2, AAV5, AAV6, AAV8, AAV9) that allows systematic comparison and selection of the optimal vector for a specific application. In our studies we observed marked differences among serotypes in the efficiency to transduce three different brain regions namely the striatum, hippocampus and neocortex of the mouse. Despite the fact that the analyzed serotypes have the general ability to transduce all major cell types in the brain (neurons, microglia, astrocytes and oligodendrocytes), the expression level of a reporter gene driven from a ubiquitous promoter varies significantly for specific cell type / serotype combinations. For example, rAAV8 is particularly efficient to drive transgene expression in astrocytes while rAAV9 appears well suited for the transduction of cortical neurons. Interestingly, we demonstrate selective retrograde transport of rAAV5 along axons projecting from the ventral part of the entorhinal cortex to the dentate gyrus. Furthermore, we show that self-complementing rAAV can be used to significantly decrease the time required for the onset of transgene expression in the mouse brain.Keywords
This publication has 70 references indexed in Scilit:
- Cell-Type-Based Analysis of MicroRNA Profiles in the Mouse BrainNeuron, 2012
- A Cre-Dependent, Anterograde Transsynaptic Viral Tracer for Mapping Output Pathways of Genetically Marked NeuronsNeuron, 2011
- Long-term Safety and Efficacy Following Systemic Administration of a Self-complementary AAV Vector Encoding Human FIX Pseudotyped With Serotype 5 and 8 Capsid ProteinsMolecular Therapy, 2011
- Start/stop signals emerge in nigrostriatal circuits during sequence learningNature, 2010
- Transneuronal circuit tracing with neurotropic virusesCurrent Opinion in Neurobiology, 2008
- Genetic Dissection of Neural CircuitsNeuron, 2008
- Tropism and toxicity of adeno-associated viral vector serotypes 1, 2, 5, 6, 7, 8, and 9 in rat neurons and glia in vitroVirology, 2008
- Monosynaptic Restriction of Transsynaptic Tracing from Single, Genetically Targeted NeuronsNeuron, 2007
- Genome-wide atlas of gene expression in the adult mouse brainNature, 2006
- Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8Molecular Therapy, 2006