Tuning up Transcription Factors for Therapy
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/8/1902 |
| _version_ | 1797570143433261056 |
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| author | Attila Becskei |
| author_facet | Attila Becskei |
| author_sort | Attila Becskei |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T20:20:44Z |
| format | Article |
| id | doaj.art-df235e7ce25a4c889dd0c5208fb3d27d |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T20:20:44Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-df235e7ce25a4c889dd0c5208fb3d27d2023-11-19T22:13:16ZengMDPI AGMolecules1420-30492020-04-01258190210.3390/molecules25081902Tuning up Transcription Factors for TherapyAttila Becskei0Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, SwitzerlandThe 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.https://www.mdpi.com/1420-3049/25/8/1902Lac repressorTet RepressorTAL-Effectortranscription activator-like effectordead Cas9homodimerization |
| spellingShingle | Attila Becskei Tuning up Transcription Factors for Therapy Molecules Lac repressor Tet Repressor TAL-Effector transcription activator-like effector dead Cas9 homodimerization |
| title | Tuning up Transcription Factors for Therapy |
| title_full | Tuning up Transcription Factors for Therapy |
| title_fullStr | Tuning up Transcription Factors for Therapy |
| title_full_unstemmed | Tuning up Transcription Factors for Therapy |
| title_short | Tuning up Transcription Factors for Therapy |
| title_sort | tuning up transcription factors for therapy |
| topic | Lac repressor Tet Repressor TAL-Effector transcription activator-like effector dead Cas9 homodimerization |
| url | https://www.mdpi.com/1420-3049/25/8/1902 |
| work_keys_str_mv | AT attilabecskei tuninguptranscriptionfactorsfortherapy |