Gene therapy in beta thalassemia: a review article

Abstract

Thalassemia is an autosomal recessive hereditary disease that occurs due to a decrease in the synthesis of Please recheck. In beta thalassemia, defects in β-globin synthesis lead to an imbalance of β- and α-globin chains and the accumulation of α4 chains in the erythroid precursor which leads to ineffective erythropoiesis, shortened red blood cell survival, and finally clinical symptoms such as delayed sexual and physical maturation, endocrine dysfunction, cardiomyopathy, liver disease, bone deformities and hepatosplenomegaly. Current treatments such as transfusion, iron chelating agents and allogeneic stem cell hematopoietic transplantation have limitations in their use, including iron overload, lack of a human leukocyte antigen (HLA) matched compatible donor, and graft versus host disease (GVHD). Gene therapy is a new therapeutic option for beta thalassemia patients that induces the continuous expression of beta globin chains in the patient’s hematopoietic stem cells. The idea of gene therapy was first proposed in the early 1970s, and the ultimate goal of this treatment method is to express the defective gene in the target cell in a way that can reduce the symptoms of the disease or eliminate them (symptoms) altogether. There are two general methods for gene therapy: the integrating vector, in which the desired gene is inserted into the genome of the target cell and its lifelong expression follows, is the non-integrating method, in which the vector doesn’t integrate into the genome of the target cell and the cytoplasmic form enables gene expression. The first beta thalassemia gene therapy was performed in France in 2006, and in this clinical trial, the first patient with the E/β0 thalassemia was treated at the age of 18. Gene therapy for beta-thalassemia has been approved by the food and drug administration in 2022 for patients aged 12 years and older who have a non β0/β0 phenotype. It seems that this therapeutic option is the definitive treatment method for blood transfusion-dependent beta-thalassemia patients.     However, this treatment method still has limitations: high cost, sensitivity of lentiviral vector production, and the possibility of integration of the vector near the proto-oncogene and its activation are some of them