Engineering Globin Gene Expression

Abstract

Hemoglobinopathies, including sickle cell disease and thalassemia, are among the most common inherited genetic diseases worldwide. Due to the relative ease of isolating and genetically modifying hematopoietic stem and progenitor cells, recent gene editing and gene therapy strategies have progressed to clinical trials with promising outcomes; however, challenges remain and necessitate the continued exploration of new gene engineering and cell transplantation protocols. Current gene engineering strategies aim at reactivating the expression of the fetal γ-globin genes in adult erythroid cells. The γ-globin proteins exhibit anti-sickling properties and can functionally replace adult β-globin. Here, we describe and compare the current genetic engineering procedures that may develop into safe and efficient therapies for hemoglobinopathies in the near future. Keywords: hemoglobin, globin, locus control region, gene therapy, gene editing, zinc finger, TALEN, CRISPR/Cas9, hematopoiesis