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Tet B or not tet B: Advances in tetracycline-inducible gene expression

1999; National Academy of Sciences; Volume: 96; Issue: 3 Linguagem: Inglês

10.1073/pnas.96.3.797

1091-6490

Helen M. Blau, Fábio Rossi,

CAR-T cell therapy research

Be it the B class, or another class of tetracycline (tet) repressor, the utility and specificity of transcriptional regulators based on this family of prokaryotic DNA binding proteins is unparalleled. A method for regulating gene expression at will in mammalian cells has long been the holy grail. Transfections of uncontrolled numbers of plasmids and unregulated gene expression were breakthroughs in the early days of molecular biology when genes encoding abundant proteins first were introduced into cultured cells. Gone are those days and those antiquated and limited methods. Fine tuning is now essential. We need systems in which gene expression can be repressed and then induced at will. Such control is essential for products that are growth inhibitory or toxic, for example, components of the apoptotic cascade. We need to be able to monitor different levels of gene expression during discrete time periods in cultured cells and in animals to understand the regulation of signal transduction that culminates in different cell fates. Cells that stably express deleterious proteins or cytokines may be lost or their phenotype altered during long-term selection. Clearly, for gene therapy, regulation is crucial. Modulating gene expression in cycles that mimic endogenous patterns is highly desirable, and avoiding toxic levels is a must.