Cell Biol Toxicol (2010) 26:1–20 neurons has been achieved using the neuron-specific synapsin promoter to drive neuronal-enriched expres- sion of polyQ proteins (Howarth et al. 2009). Lentiviral vectors have subsequently been used to create an in vivo model of polyQ disease in rat striatum (Howarth et al. 2007). The initial enthusiasm behind viral vector technologies is therefore still founded, especially in the laboratory setting where they provide a useful tool to enable the genetic manipulation of cells in vitro without the need for traditional transfection methods. The advent of lentiviral vectors has enabled the creation of ‘stable’ cell lines as well as an in vivo expression system with true longevity. In terms of gene therapy, many lessons have been learnt from clinical trials where problems of immune response and 13 insertional mutagenesis have been highlighted (Staal et al. 2008). Such difficulties are slowly being addressed, and further developments involving im- proved targeting, production, transgene expression and limitations of longevity are frequently occurring in each system. In addition, new technologies, including that of cell-based delivery of Ad vectors (Power and Bell 2007), are also driving the field forward, and certain vector systems are proving instrumental in clinical breakthroughs. Of particular note are the advances in glioma therapy utilising HSV vectors (Markert et al. 2006; Todo 2008) and the development in AAV vectors (Buning et al. 2008; Monahan and Samulski 2000), including clinical trials for retinal therapy (Buch et al. 2008). Fig. 6 Utilising viral vectors to create models of polyglutamine disease. a SBMA model in mouse neuroblastoma cell line. Transduction of mouse neuroblastoma cells, N2a’s, with adenoviral vectors expressing the androgen receptor construct that contains an expanded polyglutamine (CAG) repeat tract, leads to the development of protein aggregates within the cytoplasm upon testosterone addition. b Adenoviral vectors are used to create a model of polyglutamine in dissociated primary cortical neurons. These viruses express polyQ construct tagged with EGFP, driven by the synapsin promoter to enhance neuron-specific expression. c A similar model is also produced following the transduction of dissociated primary cortical neurons with adenoviral vectors expressing huntingtin with 103 PolyQ repeats fused to EGFP. d Lentiviral vectors expressing the polyQ-EGFP constructs are injected into rat striatum to create an in vivo model of polyglutamine disease