Gene Therapy for Sickle Cell Disease: Start of a New Era

Sickle cell disease (SCD) is the consequence of the formation of hemoglobin S (HbS), typically resulting from homozygosity or compound heterozygosity for pathogenic variants in the sickle cell gene. Under low oxygen pressure, sickle hemoglobin molecules affected by sickle cell pathogenic variants interact with one another to deform the red cell and give the cell its classic “sickle” appearance. This defect in the beta chain forms a hump that fits into another complimentary spot on another hemoglobin molecule, thereby allowing them to hook together and form tetrahedral crystals. These ridged aggregates go on to precipitate out of solution and lead to collapse of erythrocyte and result in loss of cellular function and ensuing anemia. The main determinant of cell deformation is the rate and extent of HbS formation [1].