Analysis of transduction efficiency, tropism and axonal transport of AAV serotypes 1, 2, 5, 6, 8 and 9 in the mouse brain

PLoS One. 2013 Sep 27;8(9):e76310. doi: 10.1371/journal.pone.0076310. eCollection 2013.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Axonal Transport / physiology*
  • Brain / virology*
  • Cloning, Molecular
  • Dependovirus / genetics*
  • Gene Expression Regulation / genetics
  • Gene Transfer Techniques*
  • Genetic Vectors / genetics*
  • Mice
  • Microscopy, Fluorescence
  • Organ Specificity / genetics
  • Transduction, Genetic / methods*
  • Transgenes / genetics

Grant support

The research was funded by Boehringer Ingelheim Pharmaceuticals directly (SK) or through core funding of the Research Institute of Molecular Pathology (IMP) (DFA, SR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.