Leadership In Controlled Gene Expression

The Tet Technology is used by many for-profit entities but naturally only few of these applications are publicly accessible. In the following we will briefly list some published applications by pharmaceutical and biotech companies e.g. during the drug discovery process, before focusing on industrial applications where Tet was of prime importance. As such we will review work by ‘Elitra’/’Merck’ on target identification in antifungal drug discovery, the development of cell lines by ‘Avid Therapeutics’ which are successfully used by various companies to screen compound libraries for inhibitors of viral replication. We also report on the first field trials for pest management by the British biotech company ‘Oxitec’.

Of the few published applications of the Tet Technology in the drug discovery process we would like to briefly mention work by ‘Tibotec’, a Belgian company which established an image-based high-content screening assay relying on a Tet-On cell line to identify compounds interfering with HCV replication (Berke et al., 2010). ‘Boehringer Ingelheim’ applied the Tet-Off system in screens for tyrosine kinase inhibitors (Stratowa et al. 1999). Furthermore, scientists at ‘GlaxoSmithKline’ developed a Tet-On dependent mechanistic assay to identify and characterize inhibitors of Polo-like Kinase I (Lansing et al., 2007) of importance for studies in cancerogenesis while ‘Astra-Zeneca’ employed Tet-On cell lines to determine the pharmacology of the channel encoded by wt hERG or hERG single nucleotide polymorphisms (Männikkö et al., 2010), a question of relevance for drug design in cardiac diseases.   Finally ‘CytRx’ Corporation employed the Tet Technology during a search for small molecules that act as chaperone amplifiers to treat neurodegenerative diseases (Zhou et al., 2009).