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Trends Genet. 2018 Dec;34(12):927-940. doi: 10.1016/j.tig.2018.09.004. Epub 2018 Oct 1.

Wake-up Sleepy Gene: Reactivating Fetal Globin for β-Hemoglobinopathies.

Author information

1
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.
2
School of Biotechnology and Biomolecular Sciences, University of New South Wales (UNSW) Sydney, Sydney, New South Wales, Australia.
3
School of Biotechnology and Biomolecular Sciences, University of New South Wales (UNSW) Sydney, Sydney, New South Wales, Australia; Present address: Altius Institute for Biomedical Sciences, Seattle, WA, USA.
4
School of Biotechnology and Biomolecular Sciences, University of New South Wales (UNSW) Sydney, Sydney, New South Wales, Australia. Electronic address: m.crossley@unsw.edu.au.

Abstract

Disorders 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.

KEYWORDS:

CRISPR-Cas9; genome editing; hemoglobinopathies; hereditary persistence of fetal hemoglobin; sickle cell disease; thalassemia

PMID:
30287096
DOI:
10.1016/j.tig.2018.09.004
[Indexed for MEDLINE]

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