The tetracycline-repressible (TetOFF) system has been widely used in protein pharmaceutical production and gene therapy due to its efficiency and non-toxicity in controlling transgene expression in mammalian cells. However, a limitation has been the inability to independently control the expression of a second transgene. Fussenegger and colleagues have developed a versatile and complementary system regulated by the streptogramin family of human oral antibiotics. They combined a bacterial promoter element (P_Tet) and the pristinamycin repressor, the Pip protein, with various promoters and viral transactivation domains to create both streptogramin-repressible and inducible systems that can work in combination with TetOFF in various human cell lines.The tetracycline-repressible (TetOFF) system has been widely used in protein pharmaceutical production and gene therapy due to its efficiency and non-toxicity in controlling transgene expression in mammalian cells. However, a limitation has been the inability to independently control the expression of a second transgene. Fussenegger and colleagues have developed a versatile and complementary system regulated by the streptogramin family of human oral antibiotics. They combined a bacterial promoter element (P_Tet) and the pristinamycin repressor, the Pip protein, with various promoters and viral transactivation domains to create both streptogramin-repressible and inducible systems that can work in combination with TetOFF in various human cell lines.