title: Alternative options for DNA-based experimental therapy of β-thalassemia.
abstract: BACKGROUND
  Beta-thalassemias are caused by more than 200 mutations of the β-globin gene, leading to low or absent production of adult hemoglobin. Achievements have been made with innovative therapeutic strategies for β-thalassemias, based on research conducted at the levels of gene structure, transcription, mRNA processing and protein synthesis.
  
  
  METHODS
  The objective of this review is to describe the development of therapeutic strategies employing viral and non-viral DNA-based approaches for treatment of β-thalassemia.
  
  
  CONCLUSIONS
  Modification of β-globin gene expression in β-thalassemia cells has been achieved by gene therapy, correction of the mutated β-globin gene and RNA repair. In addition, cellular therapy has been proposed for β-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 β-thalassemia, DNA-based approaches to increase HbF production have been optimized, including treatment of target cells with lentiviral vectors carrying γ-globin genes. Finally, DNA-based targeting of α-globin gene expression has been applied to reduce the excess of α-globin production by β-thalassemia cells, one of the major causes of the clinical phenotype.
authors.affiliation: University of Ferrara, Department of Biochemistry and Molecular Biology, BioPharmaNet and Laboratory for the Development of Gene and Pharmacogenomic Therapy of Thalassaemia, Ferrara, Italy. gam@unife.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D000328:Adult; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use*; D006801:Humans; D017086:beta-Thalassemia / Q000235:genetics* / Q000628:therapy*