Access to a well-validated technology for temporal- and tissue-specific gene induction or targeted gene ablation

The Tet technology was first described for in vivo use in 1995 (M. Gossen et al. Science) and consequently utilized many times to analyze the results of gene expression after the onset of a disease. Tet technology has also been used to mimic physiopathological conditions. More recently, Tet technology has been coupled to miRNA and shRNA techniques in order to temporally control knock-down of gene expression.

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• Tet-regulated mouse and rat models have a very strong track record of success (more than 7000 publications). genOway builds its new models based on past successes, maximizing model performance and reliability.

• Tet technology can be used for the development of both "on" and "off" models.

• Tet technology is constantly upgraded to provide a wide range of molecular systems useful to the development of new models. (Modifications & Refinements)

• Improved Tet technology includes repressors to diminish leakiness of the system.

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Key references substantiating the improvement of the Tet technology

Further improvement of the Tet-On system: S. Urlinger et al. PNAS 2000. Exploring the sequence space for tetracycline-dependent transcriptional activators: novel mutations yield expanded range and sensitivity.

Optimization for higher activity: X. Zhou et al. Gene Ther. 2006. Optimization of the Tet-On system for regulated gene expression through viral evolution.

Improvement to minimize background expression: R. Loew et al. BMC Biotechnol. 2010. Improved Tet-responsive promoters with minimized background expression.

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How does it work?

Tet technology comprises two complementary circuits: the tTA-dependent circuit (Tet-Off system) and the rtTA-dependent circuit (Tet-On system).

The Tet gene expression system functions when a recombinant tetracycline-controlled transcription factor (either tTA for Tet-Off or rtTA for Tet-On) binds to the Tet-op promoter, subsequently driving the expression or controlling the inhibition of the target gene (see figure below).

Gene expression is regulated by the presence or absence of tetracycline or one of its derivatives such as doxycycline. Tetracycline binds directly to the transcription factors.

Tet-Off system: tetracycline prevents the tTA transcription factor from binding DNA at the promoter. Gene expression is inhibited in the presence of tetracycline.

Tet-On system: tetracycline binds the rtTA transcription factor and allows it to bind DNA at the promoter. Gene expression is induced in the presence of tetracycline.