Sickle cell disease (SCD) is a monogenic blood disease caused by a point mutation in the gene coding for β-globin. The abnormal hemoglobin [sickle hemoglobin (HbS)] polymerizes under low-oxygen conditions and causes red blood cells to sickle. The clinical presentation varies from very severe (with acute pain, chronic pain, and early mortality) to normal (few complications and a normal life span). The variability of SCD might be due (in part) to various genetic modulators. First, we review the main genetic factors, polymorphisms, and modifier genes that influence the expression of globin or otherwise modulate the severity of SCD. Considering SCD as a complex, multifactorial disorder is important for the development of appropriate pharmacological and genetic treatments. Second, we review the characteristics, advantages, and disadvantages of the latest advances in gene therapy for SCD, from lentiviral-vector-based approaches to gene-editing strategies.

中文翻译：

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镰状细胞病：从遗传学到治疗方法

镰状细胞病 (SCD) 是一种单基因血液病，由 β-珠蛋白编码基因的点突变引起。异常血红蛋白[镰状血红蛋白（HbS）]在低氧条件下聚合，导致红细胞呈镰状。临床表现从非常严重（急性疼痛、慢性疼痛和早期死亡）到正常（很少并发症和正常寿命）不等。 SCD 的变异性可能（部分）归因于各种遗传调节剂。首先，我们回顾了影响珠蛋白表达或以其他方式调节 SCD 严重程度的主要遗传因素、多态性和修饰基因。将 SCD 视为一种复杂的多因素疾病对于开发适当的药理学和遗传治疗非常重要。其次，我们回顾了 SCD 基因治疗最新进展的特点、优点和缺点，从基于慢病毒载体的方法到基因编辑策略。