β-Hemoglobinopathies are the most common monogenic disorders, and a century of research has provided us with a better understanding of the attributes of these diseases. Allogenic stem cell transplantation was the only potentially curative option available for these diseases until the discovery of gene therapy. The findings on the protective nature of fetal hemoglobin in sickle cell disease (SCD) and thalassemia patients carrying hereditary persistence of fetal hemoglobin (HPFH) mutations has given us the best evidence that the cure for β-hemoglobinopathies remains hidden in the hemoglobin locus. The detailed understanding of the developmental gene regulation of gamma-globin (γ-globin) and the emergence of gene manipulation strategies offer us the opportunity for developing a γ-globin gene-modified autologous stem cell transplantation therapy. In this review, we summarize different therapeutic strategies that reactivate fetal hemoglobin for the gene therapy of β-hemoglobinopathies.

中文翻译：

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发育性伽马珠蛋白基因表达的调控：治疗血红蛋白病的方法

β-血红蛋白病是最常见的单基因疾病，一个世纪的研究使我们对这些疾病的属性有了更好的了解。在发现基因疗法之前，同种异体干细胞移植是治疗这些疾病的唯一潜在治疗选择。关于携带遗传性持续性胎儿血红蛋白 (HPFH) 突变的镰状细胞病 (SCD) 和地中海贫血患者中胎儿血红蛋白的保护性质的研究结果为我们提供了最好的证据，证明β-血红蛋白病的治愈方法仍然隐藏在血红蛋白基因座中。对γ-球蛋白（γ-球蛋白）发育基因调控的详细了解以及基因操作策略的出现为我们开发γ-球蛋白基因修饰的自体干细胞移植疗法提供了机会。在这篇综述中，我们总结了重新激活胎儿血红蛋白用于β-血红蛋白病基因治疗的不同治疗策略。