• Beeke Wienert, Gabriella E Martyn, Alister P W Funnell, Kate G R Quinlan, and Merlin Crossley.
• School of Biotechnology and Biomolecular Sciences, University of New South Wales (UNSW) Sydney, Sydney, New South Wales, Australia; Innovative Genomics Institute, University of California, Berkeley, CA, USA; Present address: Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
• Trends Genet. 2018 Dec 1; 34 (12): 927-940.

AbstractDisorders in hemoglobin (hemoglobinopathies) were the first monogenic diseases to be characterized and remain among the most common and best understood genetic conditions. Moreover, the study of the β-globin locus provides a textbook example of developmental gene regulation. The fetal γ-globin genes (HBG1/HBG2) are ordinarily silenced around birth, whereupon their expression is replaced by the adult β-globin genes (HBB primarily and HBD). Over 50 years ago it was recognized that mutations that cause lifelong persistence of fetal γ-globin expression ameliorate the debilitating effects of mutations in β-globin. Since then, research has focused on therapeutically reactivating the fetal γ-globin genes. Here, we summarize recent discoveries, focusing on the influence of genome editing technologies, including CRISPR-Cas9, and emerging gene therapy approaches.Copyright © 2018 Elsevier Ltd. All rights reserved.

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