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Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia

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Gene and Cell Therapies for Beta-Globinopathies

Part of the book series: Advances in Experimental Medicine and Biology ((ASGCT,volume 1013))

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.

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Acknowledgements

This work is supported by the Children’s Cancer and Blood Foundation and NIH grant NHLBI-R01HL102449-03 (to S. Rivella)

Competing Interests

S. Rivella is a consultant for Novartis, Biomarin and Isis Pharmaceuticals. In addition, he is a co-inventor for the patents US8058061 B2 C12N 20111115 and US7541179 B2C12N 20090602. The consulting work and intellectual property of S. Rivella did not affect in any way the design, conduct, or reporting of this research.

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, 515 E. 71st St., Room S-709, New York, NY, 10021, USA

    Alisa C. Dong

  2. Division of Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, 515 E. 71st St., S702, Box 284, New York, NY, 10021, USA

    Stefano Rivella

Authors
  1. Alisa C. Dong
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  2. Stefano Rivella
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Correspondence to Stefano Rivella .

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Editors and Affiliations

  1. Cincinnati Children’s Hospital, Comprehensive Sickle Cell Program, Cincinnati, Ohio, USA

    Punam Malik

  2. National Institutes of Health and Human Services, Bethesda, Maryland, USA

    John Tisdale

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Dong, A.C., Rivella, S. (2017). Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia. In: Malik, P., Tisdale, J. (eds) Gene and Cell Therapies for Beta-Globinopathies. Advances in Experimental Medicine and Biology(), vol 1013. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7299-9_6

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