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Adv Exp Med Biol. 2017;1013:155-176. doi: 10.1007/978-1-4939-7299-9_6.

Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia.

Author information

1
Division of Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, 515 E. 71st St., Room S-709, New York, NY, 10021, USA.
2
Division of Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, 515 E. 71st St., S702, Box 284, New York, NY, 10021, USA. str2010@med.cornell.edu.

Abstract

Beta-thalassemia and sickle cell anemia are two of the most common diseases related to the hemoglobin protein. In these diseases, the beta-globin gene is mutated, causing severe anemia and ineffective erythropoiesis. Patients can additionally present with a number of life-threatening co-morbidities, such as stroke or spontaneous fractures. Current treatment involves transfusion and iron chelation; allogeneic bone marrow transplant is the only curative option, but is limited by the availability of matching donors and graft-versus-host disease. As these two diseases are monogenic diseases, they make an attractive setting for gene therapy. Gene therapy aims to correct the mutated beta-globin gene or add back a functional copy of beta- or gamma-globin. Initial gene therapy work was done with oncoretroviral vectors, but has since shifted to lentiviral vectors. Currently, there are a few clinical trials underway to test the curative potential of some of these lentiviral vectors. This review will highlight the work done thus far, and present the challenges still facing gene therapy, such as genome toxicity concerns and achieving sufficient transgene expression to cure those with the most severe forms of thalassemia.

KEYWORDS:

Beta-thalassemia; Cell-based therapy; Gene therapy; Hematopoietic stem cells; Hemoglobin disorders; Hemoglobinopathies; Lentivirus; Mixed chimerism; Oncoretrovirus; Sickle cell anemia

PMID:
29127680
PMCID:
PMC5718882
DOI:
10.1007/978-1-4939-7299-9_6
[Indexed for MEDLINE]
Free PMC Article

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