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Gene Therapy in Thalassemia and Hemoglobinopathies

Sickle cell disease (SCD) and ß-thalassemia represent the most common hemoglobinopathies caused, respectively, by the alteration of structural features or deficient production of the ß-chain of the Hb molecule. Other hemoglobinopathies are characterized by different mutations in the α- or ß-globin g...

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Detalles Bibliográficos
Autores principales: Breda, Laura, Gambari, Roberto, Rivella, Stefano
Formato: Texto
Lenguaje:English
Publicado: Università Cattolica del Sacro Cuore 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033156/
https://www.ncbi.nlm.nih.gov/pubmed/21415990
http://dx.doi.org/10.4084/MJHID.2009.008
Descripción
Sumario:Sickle cell disease (SCD) and ß-thalassemia represent the most common hemoglobinopathies caused, respectively, by the alteration of structural features or deficient production of the ß-chain of the Hb molecule. Other hemoglobinopathies are characterized by different mutations in the α- or ß-globin genes and are associated with anemia and might require periodic or chronic blood transfusions. Therefore, ß-thalassemia, SCD and other hemoglobinopathies are excellent candidates for genetic approaches since they are monogenic disorders and, potentially, could be cured by introducing or correcting a single gene into the hematopoietic compartment or a single stem cell. Initial attempts at gene transfer of these hemoglobinopathies have proved unsuccessful due to limitations of available gene transfer vectors. With the advent of lentiviral vectors many of the initial limitations have been overcame. New approaches have also focused on targeting the specific mutation in the ß-globin genes, correcting the DNA sequence or manipulating the fate of RNA translation and splicing to restore ß-globin chain synthesis. These techniques have the potential to correct the defect into hematopoietic stem cells or be utilized to modify stem cells generated from patients affected by these disorders. This review discusses gene therapy strategies for the hemoglobinopathies, including the use of lentiviral vectors, generation of induced pluripotent stem cells (iPS) cells, gene targeting, splice-switching and stop codon readthrough.