Gene Therapy as the New Frontier for Sickle Cell Disease

Abstract

: Sickle Cell Disease (SCD) is one of the most common monogenic disorders caused by a point mutation in the β-globin gene. This mutation results in polymerization of hemoglobin (Hb) under reduced oxygenation conditions, causing rigid sickle-shaped RBCs and hemolytic anemia. This clearly defined fundamental molecular mechanism makes SCD a prototypical target for precision therapy. Both the mutant β-globin protein and its down-stream pathophysiology are pharmacological targets of intensive research. SCD also is a disease well-suited for biological interventions like gene therapy. Recent advances in hem-atopoietic stem cell (HSC) transplantation and gene therapy platforms, like Lentiviral vec-tors and gene editing strategies, expand the potentially curative options for patients with SCD. This review discusses the recent advances in precision therapy for SCD and the pre-clinical and clinical advances in autologous HSC gene therapy for SCD.