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Treating hemoglobinopathies using gene-correction approaches: promises and challenges

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Abstract

Hemoglobinopathies are genetic disorders caused by aberrant hemoglobin expression or structure changes, resulting in severe mortality and health disparities worldwide. Sickle cell disease (SCD) and β-thalassemia, the most common forms of hemoglobinopathies, are typically treated using transfusions and pharmacological agents. Allogeneic hematopoietic stem cell transplantation is the only curative therapy, but has limited clinical applicability. Although gene therapy approaches have been proposed based on the insertion and forced expression of wild-type or anti-sickling β-globin variants, safety concerns may impede their clinical application. A novel curative approach is nuclease-based gene correction, which involves the application of precision genome-editing tools to correct the disease-causing mutation. This review describes the development and potential application of gene therapy and precision genome-editing approaches for treating SCD and β-thalassemia. The opportunities and challenges in advancing a curative therapy for hemoglobinopathies are also discussed.

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Acknowledgments

This work was supported by the National Institutes of Health as an NIH Nanomedicine Development Center Award (PN2EY018244 to GB) and by the Cancer Prevention and Research Institute of Texas (RR140081 to GB).

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  1. Bioengineering Program, Clemson University and Medical University of South Carolina, Charleston, SC, 29425, USA

    Renee N. Cottle

  2. Department of Bioengineering, Rice University, Houston, TX, 77030, USA

    Ciaran M. Lee & Gang Bao

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Cottle, R.N., Lee, C.M. & Bao, G. Treating hemoglobinopathies using gene-correction approaches: promises and challenges. Hum Genet 135, 993–1010 (2016). https://doi.org/10.1007/s00439-016-1696-0

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