The β-thalassemias are a group of hereditary diseases caused by more than 300 mutations of the adult β-globin gene, leading to low or absent production of adult hemoglobin (HbA) (1-3). Together with sickle cell anemia (SCA), thalassemia syndromes are among the most impactful diseases in developing countries, in which the lack of genetic counselling and prenatal diagnosis have contributed to the maintenance of a very high frequency in the population. The management of β-thalassemia patients is mostly based on blood transfusion, chelation therapy and, alternatively, on bone marrow transplantation (2). Recently, novel therapeutic options have been explored, such as gene therapy (3) and fetal hemoglobin (HbF) induction (4). Despite the fact that these approaches are promising, they are at present still under deep experimental development and limited to a low number of clinical trials (2-4). With respect to gene therapy for β-thalassemia significant progresses are expected, also considering fundamental insights into globin switching and new technology developments which might have a strong impact on novel gene-therapy approaches (3). A robust information is however available regarding the management of β-thalassemia, i.e., that patients exhibiting high levels of endogenous HbF might exhibit a milder clinical status, as in the case of hereditary persistence of fetal hemoglobin (HPFH) (4). In this context, one of the most exciting strategies recently proposed for hereditary diseases, including β-thalassemia, is genome editing using a variety of strongly validated approaches. Among these strategies, the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 nuclease system (5-7), in which a single guide RNA (sgRNA) directs the Cas9 nuclease for site-specific cleavage, is considered the most efficient.

Ground state naïve pluripotent stem cells and CRISPR/Cas9 gene correction for β-thalassemia

FINOTTI, Alessia;BORGATTI, Monica;GAMBARI, Roberto
2016

Abstract

The β-thalassemias are a group of hereditary diseases caused by more than 300 mutations of the adult β-globin gene, leading to low or absent production of adult hemoglobin (HbA) (1-3). Together with sickle cell anemia (SCA), thalassemia syndromes are among the most impactful diseases in developing countries, in which the lack of genetic counselling and prenatal diagnosis have contributed to the maintenance of a very high frequency in the population. The management of β-thalassemia patients is mostly based on blood transfusion, chelation therapy and, alternatively, on bone marrow transplantation (2). Recently, novel therapeutic options have been explored, such as gene therapy (3) and fetal hemoglobin (HbF) induction (4). Despite the fact that these approaches are promising, they are at present still under deep experimental development and limited to a low number of clinical trials (2-4). With respect to gene therapy for β-thalassemia significant progresses are expected, also considering fundamental insights into globin switching and new technology developments which might have a strong impact on novel gene-therapy approaches (3). A robust information is however available regarding the management of β-thalassemia, i.e., that patients exhibiting high levels of endogenous HbF might exhibit a milder clinical status, as in the case of hereditary persistence of fetal hemoglobin (HPFH) (4). In this context, one of the most exciting strategies recently proposed for hereditary diseases, including β-thalassemia, is genome editing using a variety of strongly validated approaches. Among these strategies, the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 nuclease system (5-7), in which a single guide RNA (sgRNA) directs the Cas9 nuclease for site-specific cleavage, is considered the most efficient.
Finotti, Alessia; Borgatti, Monica; Gambari, Roberto
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/2368344
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