12 kinase (MCK), phosphoglycerate kinase and neuronal- specific enolase (NSE). Muscle-specific expression has been achieved using the MCK promoter in both adenoviral and lentiviral systems (Ferrari et al. 1995; Larochelle et al. 1997). AAV9 vectors containing the Desmin promoter have also been used to produce gene expression in cardiac and skeletal muscle following systemic vector administration (Pacak et al. 2008). Bone-specific expression has been achieved using the murine leukaemia virus long terminal repeat promoter (RhMLV; Phillips et al. 2007) or the human osteogenic promoter osteocalcin (Kofron and Laurencin 2006). One major field of research has focused on brain- specific expression. Several promoters have been tested for targeting to the CNS using AAV vectors (Terzi and Zachariou 2008). These include CMV, NSE, platelet- derived growth factor-b and CMV-chicken β-actin (Shevtsova et al. 2005). Similar studies have been performed using Ad and lentiviral vectors (Jakobsson et al. 2003; Virta et al. 2006). Cell specificity achieved by particular promoters can vary between different CNS regions (Peel et al. 1997). GFAP promoter has been shown to drive exclusive transduction in spinal cord, hippocampal and striatal neurons. The synapsin promoter has also been utilised in Ad, lentiviral and AAV vectors systems to drive neuron-specific expres- sion (Glover et al. 2003; Nathanson et al. 2009; Peel et al. 1997; Sims et al. 2008; Fig. 5). Viral vector utility has also been improved by the incorporation of regulatable expression systems, such as tetracycline (Harding et al. 1998) and RU486 (Burcin et al. 1999) inducible systems. Tetracycline inducible systems have produced highly regulatable Cell Biol Toxicol (2010) 26:1–20 Ad vectors (Harding et al. 1997, 1998), allowing transgene expression to be switched on and off in vivo by the simple addition of doxycycline (a tetracycline analog) in drinking water. Such systems can enable the production of vectors that contain toxic inserts, acting specifically and at high levels in the “On” state, and show dose-responsive expression allowing varied levels of gene expression. Subsequent studies have combined this system with cell-specific promoters to drive neuron-specific and glial-specific regulatable transgene expression (Glover et al. 2002, 2003; Lee et al. 2005; Ralph et al. 2000). The well- characterised tetracycline-based regulatable systems have also been utilised in lentiviral vector design (Kafri et al. 2000) and AAV-based studies (Stieger et al. 2009). Such lentiviral systems have already been used to mediate regulated delivery of genes thought to alleviate symptoms of Parkinson’s disease (Georgievska et al. 2004; Vogel et al. 2004). A range of viral vectors are therefore available to aid research, each suited for different purposes/applications due to their individual characteristics. Ad vectors have been greatly utilised for in vitro studies, transferring genetic material into many cell lines and cultured cell systems. Within our laboratory, they have been utilised to generate in vitro models of polyglutamine diseases in both a mouse neuroblastoma cell line and primary neurons (Fig. 6). Viral-mediated gene transfer enables the production of dose-dependant models where the level of disease protein expression (and therefore the severity of the disease state) can be modified by viral dose as well as the length of the CAG repeat tract within the expressed transgene. Expression within primary Fig. 5 Neuron-specific expression using the synapsin promoter. Modification of adenoviral vectors using tissue-specific pro- moters to produce specific expression in embryonic rat organo- typic brain cultures: a Ad-CMV-EGFP results in ubiquitous expression. b Ad-Syn-EGFP vectors, containing the human synapsin promoter, produces neuron-specific expression