Gene editing for sickle cell disease and transfusion dependent thalassemias- A cure within reach

Sickle cell disease (SCD) is associated with significant morbidity and shortened life expectancy. Similarly, patients with transfusion dependent beta thalassemia (TdT) require life-long transfusion therapy, chela-tion therapy and significant organ dysfunction. Allogeneic transplantation from a matched family donor provided the only curative option for patients with SCD and TdT. Unfortunately, less than 20% of patients have a fully matched related donor and results using unrelated donor transplant were associated with high rate of complications. Ex vivo gene therapy through globin gene addition has been investigated ex-tensively and recent encouraging preliminary data resulted in regulatory approval in patients with TdT. Recent improvements in our understanding of the molecular pathways controlling erythropoiesis and globin switching from fetal hemoglobin to adult hemoglobin offer a new and exciting therapeutic options. Rapid and substantial advances in genome editing tools using CRISPR/Cas9, have raised the possibility of genetic editing and correction in patient derived hematopoietic stem and progenitor cells. We will review results of gene editing approach that can induce fetal hemoglobin production in patients with SCD and TdT.(c) 2023 Elsevier Inc. All rights reserved.

Automated summary

Sickle cell disease and transfusion dependent beta thalassemia are associated with high morbidity and shortened life expectancy. Allogeneic transplantation remains the only curative option, but finding fully matched related donors is difficult. However, recent advances in ex vivo gene therapy and genome editing offer new and promising therapeutic options.