Hemoglobin is a tetrameric protein composed of two α and two β chains, each containing a heme group that reversibly binds oxygen. The composition of hemoglobin changes during development in order to fulfill the need of the growing organism, stably maintaining a balanced production of α-like and β-like chains in a 1:1 ratio. Adult hemoglobin (HbA) is composed of two α and two β subunits (α2β2 tetramer), whereas fetal hemoglobin (HbF) is composed of two γ and two α subunits (α2γ2 tetramer). Qualitative or quantitative defects in β-globin production cause two of the most common monogenic-inherited disorders: β-thalassemia and sickle cell disease. The high frequency of these diseases and the relative accessibility of hematopoietic stem cells make them an ideal candidate for therapeutic interventions based on genome editing. These strategies move in two directions: the correction of the disease-causing mutation and the reactivation of the expression of HbF in adult cells, in the attempt to recreate the effect of hereditary persistence of fetal hemoglobin (HPFH) natural mutations, which mitigate the severity of β-hemoglobinopathies. Both lines of research rely on the knowledge gained so far on the regulatory mechanisms controlling the differential expression of globin genes during development.

Barbarani, G., Łabedz, A., Ronchi, A. (2020). β-Hemoglobinopathies: The Test Bench for Genome Editing-Based Therapeutic Strategies. FRONTIERS IN GENOME EDITING, 2 [10.3389/fgeed.2020.571239].

β-Hemoglobinopathies: The Test Bench for Genome Editing-Based Therapeutic Strategies

Barbarani, Gloria
Primo
;
Ronchi, Antonella Ellena
Ultimo
2020

Abstract

Hemoglobin is a tetrameric protein composed of two α and two β chains, each containing a heme group that reversibly binds oxygen. The composition of hemoglobin changes during development in order to fulfill the need of the growing organism, stably maintaining a balanced production of α-like and β-like chains in a 1:1 ratio. Adult hemoglobin (HbA) is composed of two α and two β subunits (α2β2 tetramer), whereas fetal hemoglobin (HbF) is composed of two γ and two α subunits (α2γ2 tetramer). Qualitative or quantitative defects in β-globin production cause two of the most common monogenic-inherited disorders: β-thalassemia and sickle cell disease. The high frequency of these diseases and the relative accessibility of hematopoietic stem cells make them an ideal candidate for therapeutic interventions based on genome editing. These strategies move in two directions: the correction of the disease-causing mutation and the reactivation of the expression of HbF in adult cells, in the attempt to recreate the effect of hereditary persistence of fetal hemoglobin (HPFH) natural mutations, which mitigate the severity of β-hemoglobinopathies. Both lines of research rely on the knowledge gained so far on the regulatory mechanisms controlling the differential expression of globin genes during development.
Articolo in rivista - Review Essay
genome editing; globin genes; hereditary persistence of fetal hemoglobin; programmable endonucleases; β-hemoglobinopathies;
English
2020
2
571239
open
Barbarani, G., Łabedz, A., Ronchi, A. (2020). β-Hemoglobinopathies: The Test Bench for Genome Editing-Based Therapeutic Strategies. FRONTIERS IN GENOME EDITING, 2 [10.3389/fgeed.2020.571239].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/335899
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