Using Recombinant Adeno-Associated Viral Vectors for Gene Expression in the Brain

Recombinant AAV vectors currently enjoy an excellent track record in brain applications such as generating preclinical models of neurodegeneration and gene therapy for brain disorders. Indeed, rAAV vectors have been useful in modeling diseases such as Parkinson’s disease (discussed below) and have also been tested in various phases of clinical development for Parkinson’s disease (Christine et al., Neurology 73:1662–1669, 2009; Kaplitt et al., Lancet 369:2097–2105, 2007) and Alzheimer’s disease (Mandel 2010, Curr Opin Mol Ther 12:240–247, 2010). In this review, we will discuss the vectorology of rAAV, rAAV production, and purification of the different rAAV serotypes. We will also describe locoregional transduction of the brain using rAAV vectors and illustrate these techniques with specific examples of applications such as non-invasive imaging of reporter genes and disease modeling in Parkinson’s disease.