Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Tuning up Transcription Factors for Therapy

Version 1 : Received: 28 February 2020 / Approved: 29 February 2020 / Online: 29 February 2020 (09:13:12 CET)

A peer-reviewed article of this Preprint also exists.

Becskei, A. Tuning up Transcription Factors for Therapy. Molecules 2020, 25, 1902. Becskei, A. Tuning up Transcription Factors for Therapy. Molecules 2020, 25, 1902.


The recent developments in the delivery and design of transcription factors put their therapeutic applications within reach, exemplified by cell replacement, cancer differentiation and T-cell based cancer therapies. The success of such applications depends on the efficacy and precision in the action of transcription factors. The biophysical and genetic characterization of the paradigmatic prokaryotic repressors, LacI and TetR and the designer transcription factors, TALE and CRISPR-Cas9 revealed common rules, which can help the optimization of activators and repressors. Further studies will be required to analyze the linkage between dissociation constants and enzymatic activity, the role of phase separation and squelching in activation and repression, and the long-range interaction of transcription factors with epigenetic regulators in the context of the chromosomes. Understanding these mechanisms will help to tailor systematically optimized designer transcription factors to the needs of specific applications.


LacI; Lac repressor; TetR; TAL-Effector; transcription activator-like effector; Cas9d; dissociation rate constant


Biology and Life Sciences, Biophysics

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