Sickle Cell Disease: From Genetics to Curative Approaches

Sickle cell disease (SCD) is a monogenic blood disease caused by a point mutation in the gene coding for beta-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.

Automated summary

Sickle cell disease is a blood disorder caused by a single gene mutation that leads to the production of abnormal hemoglobin. The severity of the disease varies among individuals, and it is influenced by various genetic factors and modifiers. Understanding the complex nature of the disease is important for developing effective pharmacological and genetic treatments, such as gene therapy.