Gene Therapy for Hemoglobinopathies: Beta-Thalassemia, Sickle Cell Disease

Abstract

β-thalassemia and sickle cell disease (SCD) are the most common monogenic diseases in the world and are potentially curable after allogeneic hematopoietic stem cell transplantation (HSCT) or autologous HSCT after genetic modification. Autologous gene therapy has the potential to offer a universal cure that overcomes many limitations of allogeneic HSCT including the lack of available donors, graft-vs-host disease, and graft rejection. Significant progress in gene therapy for the hemoglobinopathies has been made over the last several decades, now with multiple ongoing clinical trials investigating both gene addition and gene-editing strategies. Available results from a small number of patients, some with relatively short follow-up, are promising, with current efforts focused on continuing to improve the efficacy, durability, and safety of gene therapies for the cure of hemoglobin disorders.