Genome editing to correct a defective β-globin gene or induce fetal globin (HbF) for patients with beta-hemoglobinopathies has the potential to be a curative strategy available to all. HbF reactivation has long been an area of intense interest given the HbF inhibition of sickle hemoglobin (HbS) polymerization. Patients with HbS who also have high HbF tend to have less severe or even minimal clinical manifestations. Approaches to genetically engineer high HbF include de novo generation of naturally occurring hereditary persistence of fetal hemoglobin (HPFH) mutations, editing of transcriptional HbF repressors or their binding sites and/or regulating epigenetic intermediates controlling HbF expression. Recent preclinical and early clinical trial data show encouraging results; however, long-term follow-up is lacking, and the safety and efficacy concerns of genome editing remain.

中文翻译：

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β-血红蛋白病中胎儿血红蛋白诱导的基因组编辑策略。

基因组编辑以纠正有缺陷的 β-珠蛋白基因或诱导 β-血红蛋白病患者的胎儿珠蛋白 (HbF) 有可能成为所有人都可以使用的治疗策略。鉴于 HbF 抑制镰状血红蛋白 (HbS) 聚合，HbF 再激活长期以来一直是一个备受关注的领域。同时具有高 HbF 的 HbS 患者往往具有较轻甚至轻微的临床表现。基因工程高 HbF 的方法包括从头产生自然发生的遗传性胎儿血红蛋白 (HPFH) 突变的遗传持久性，编辑转录 HbF 抑制因子或其结合位点和/或调节控制 HbF 表达的表观遗传中间体。最近的临床前和早期临床试验数据显示出令人鼓舞的结果；然而，缺乏长期随访，基因组编辑的安全性和有效性问题仍然存在。