Alternative options for DNA-based experimental therapy of β-thalassemia

Introduction: Beta-thalassemias are caused by more than 200 mutations of the beta-globin gene, leading to low or absent production of adult hemoglobin. Achievements have been made with innovative therapeutic strategies for beta-thalassemias, based on research conducted at the levels of gene structure, transcription, mRNA processing and protein synthesis. Areas covered: The objective of this review is to describe the development of therapeutic strategies employing viral and non-viral DNA-based approaches for treatment of beta-thalassemia. Expert opinion: Modification of beta-globin gene expression in beta-thalassemia cells has been achieved by gene therapy, correction of the mutated beta-globin gene and RNA repair. In addition, cellular therapy has been proposed for beta-thalassemia, including reprogramming of somatic cells to generate induced pluripotent stem cells to be genetically corrected. Based on the concept that increased production of fetal hemoglobin (HbF) is beneficial in beta-thalassemia, DNA-based approaches to increase HbF production have been optimized, including treatment of target cells with lentiviral vectors carrying gamma-globin genes. Finally, DNA-based targeting of alpha-globin gene expression has been applied to reduce the excess of alpha-globin production by beta-thalassemia cells, one of the major causes of the clinical phenotype.