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P-TEFb as A Promising Therapeutic Target
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Tuning up Transcription Factors for Therapy

Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland
Academic Editor: Takaomi Sanda
Molecules 2020, 25(8), 1902; https://doi.org/10.3390/molecules25081902
Received: 28 February 2020 / Revised: 16 April 2020 / Accepted: 17 April 2020 / Published: 20 April 2020
(This article belongs to the Special Issue Transcription Factors as Therapeutic Targets II)
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, transcription activator-like effector (TALE) and CRISPR-dCas9 revealed common principles behind their efficacy, which can aid the optimization of transcriptional 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 natural and synthetic transcription factors to the needs of specific applications. View Full-Text
Keywords: Lac repressor; Tet Repressor; TAL-Effector; transcription activator-like effector; dead Cas9; homodimerization; aggregation; dissociation rate constant Lac repressor; Tet Repressor; TAL-Effector; transcription activator-like effector; dead Cas9; homodimerization; aggregation; dissociation rate constant
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Becskei, A. Tuning up Transcription Factors for Therapy. Molecules 2020, 25, 1902.

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