The genetic basis of sickle cell disease (SCD) was elucidated >60 years ago, yet current therapy does not rely on this knowledge. Recent advances raise prospects for improved, and perhaps curative, treatment. First, transcription factors, BCL11A and LRF/ZBTB7A, that mediate silencing of the β-like fetal (γ-) globin gene after birth have been identified and demonstrated to act at the γ-globin promoters, precisely at recognition sequences disrupted in rare individuals with hereditary persistence of fetal hemoglobin. Second, transformative advances in gene editing and progress in lentiviral gene therapy provide diverse opportunities for genetic strategies to cure SCD. Approaches include hematopoietic gene therapy by globin gene addition, gene editing to correct the SCD mutation, and genetic manipulations to enhance fetal hemoglobin production, a potent modifier of the clinical phenotype. Clinical trials may soon identify efficacious and safe genetic approaches to the ultimate goal of cure for SCD.

中文翻译：

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镰状细胞疾病的新兴遗传疗法。

镰状细胞病（SCD）的遗传学基础已于60年前阐明，但目前的治疗方法并不依赖于此知识。最近的进展为改善治疗方法提供了前景。首先，已经确定了介导出生后β样胎儿（γ-）珠蛋白基因沉默的转录因子BCL11A和LRF / ZBTB7A，并证明它们在γ珠蛋白启动子上起作用，确切地说是在稀有个体中破坏的识别序列上起作用。具有胎儿血红蛋白的遗传性持久性。其次，基因编辑的变革性进展和慢病毒基因治疗的进展为治愈SCD的遗传策略提供了多种机会。方法包括通过添加球蛋白基因进行造血基因治疗，纠正SCD突变的基因编辑以及增强胎儿血红蛋白生成的基因操作，临床表型的有效修饰剂。临床试验可能很快会确定有效且安全的遗传方法，以达到治愈SCD的最终目标。