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Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin

The level of fetal hemoglobin (HbF) is an important disease modifier for β‐thalassemia and sickle cell disease patients. Indeed, genetic tinkering with the HbF repression machinery has demonstrated great potential for disease mitigation. Such genetic treatments are costly and the high incidence of β...

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Autores principales: J. Verheul, Thijs C., Trinh, Van Tuan, Vázquez, Olalla, Philipsen, Sjaak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756256/
https://www.ncbi.nlm.nih.gov/pubmed/33002296
http://dx.doi.org/10.1002/cmdc.202000574
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author J. Verheul, Thijs C.
Trinh, Van Tuan
Vázquez, Olalla
Philipsen, Sjaak
author_facet J. Verheul, Thijs C.
Trinh, Van Tuan
Vázquez, Olalla
Philipsen, Sjaak
author_sort J. Verheul, Thijs C.
collection PubMed
description The level of fetal hemoglobin (HbF) is an important disease modifier for β‐thalassemia and sickle cell disease patients. Indeed, genetic tinkering with the HbF repression machinery has demonstrated great potential for disease mitigation. Such genetic treatments are costly and the high incidence of β‐hemoglobinopathies in low‐income countries, therefore, calls for the development of affordable, off‐the‐shelf, oral treatments. The use of PROTAC (PRoteolysis TArgeting Chimeras) technology to influence the epigenetic mechanisms involved in HbF suppression may provide a solution. In this minireview, we briefly explain the HbF repression network highlighting the epigenetic factors that could be targeted for degradation by PROTACs. We hope that this review will inspire clinicians, molecular and chemical biologists to collaborate and contribute to this fascinating field, which should ultimately deliver drugs that reactivate HbF expression with high specificity and low toxicity.
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spelling pubmed-77562562020-12-28 Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin J. Verheul, Thijs C. Trinh, Van Tuan Vázquez, Olalla Philipsen, Sjaak ChemMedChem Minireviews The level of fetal hemoglobin (HbF) is an important disease modifier for β‐thalassemia and sickle cell disease patients. Indeed, genetic tinkering with the HbF repression machinery has demonstrated great potential for disease mitigation. Such genetic treatments are costly and the high incidence of β‐hemoglobinopathies in low‐income countries, therefore, calls for the development of affordable, off‐the‐shelf, oral treatments. The use of PROTAC (PRoteolysis TArgeting Chimeras) technology to influence the epigenetic mechanisms involved in HbF suppression may provide a solution. In this minireview, we briefly explain the HbF repression network highlighting the epigenetic factors that could be targeted for degradation by PROTACs. We hope that this review will inspire clinicians, molecular and chemical biologists to collaborate and contribute to this fascinating field, which should ultimately deliver drugs that reactivate HbF expression with high specificity and low toxicity. John Wiley and Sons Inc. 2020-11-04 2020-12-15 /pmc/articles/PMC7756256/ /pubmed/33002296 http://dx.doi.org/10.1002/cmdc.202000574 Text en © 2020 The Authors. ChemMedChem published by Wiley-VCH GmbH This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Minireviews
J. Verheul, Thijs C.
Trinh, Van Tuan
Vázquez, Olalla
Philipsen, Sjaak
Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin
title Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin
title_full Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin
title_fullStr Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin
title_full_unstemmed Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin
title_short Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin
title_sort targeted protein degradation as a promising tool for epigenetic upregulation of fetal hemoglobin
topic Minireviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756256/
https://www.ncbi.nlm.nih.gov/pubmed/33002296
http://dx.doi.org/10.1002/cmdc.202000574
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