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

Publication date: Available online 1 October 2018Source: Trends in GeneticsAuthor(s): Beeke Wienert, Gabriella E. Martyn, Alister P.W. Funnell, Kate G.R. Quinlan, Merlin CrossleyDisorders 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.

Source: Trends in Genetics - October 5, 2018 Category: Genetics & Stem Cells Source Type: research