Beta (β)-thalassemia is a group of human inherited abnormalities caused by various molecular defects, which involves a decrease or cessation in the balanced synthesis of the β-globin chains in hemoglobin structure. Traditional treatment for β-thalassemia major is allogeneic bone marrow transplantation (BMT) from a completely matched donor. The limited number of human leukocyte antigen (HLA)-matched donors, long-term use of immunosuppressive regimen and higher risk of immunological complications have limited the application of this therapeutic approach. Furthermore, despite improvements in transfusion practices and chelation treatment, many lingering challenges have encouraged researchers to develop newer therapeutic strategies such as nanomedicine and gene editing. One of the most powerful arms of genetic manipulation is gene editing tools, including transcription activator-like effector nucleases, zinc-finger nucleases, and clustered regularly interspaced short palindromic repeat-Cas-associated nucleases. These tools have concentrated on γ- or β-globin addition, regulating the transcription factors involved in expression of endogenous γ-globin such as KLF1, silencing of γ-globin inhibitors including BCL11A, SOX6, and LRF/ZBTB7A, and gene repair strategies. In this review article, we present a systematic overview of the appliances of gene editing tools for β-thalassemia treatment and paving the way for patients' therapy.

Applied Physiology Research Center Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan 73461 81746 Iran

Biosensor Research Center School of Advanced Technologies in Medicine Isfahan University of Medical Sciences Isfahan 73461 81746 Iran

Cancer Prevention Research Isfahan University of Medical Sciences Isfahan 73461 81746 Iran

Department of Biomaterials Nanotechnology and Tissue Engineering School of Advanced Technologies in Medicine Isfahan University of Medical Sciences Isfahan 73461 81746 Iran

Department of Biomedical Engineering Faculty of Engineering and Natural Sciences Istinye University Sariyer Istanbul 34396 Turkey

Department of Genetics and Molecular Biology School of Medicine Isfahan University of Medical Sciences Isfahan 73461 81746 Iran

Erythron Genetics and Pathobiology Laboratory Department of Immunology Isfahan 76351 81647 Iran

Infectious Diseases and Tropical Medicine Research Center Isfahan University of Medical Sciences Isfahan 73461 81746 Iran

Isfahan Cardiovascular Research Center Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan 81583 88994 Iran

Regional Centre of Advanced Technologies and Materials Department of Physical Chemistry Faculty of Science Palacky University Šlechtitelů 27 783 71 Olomouc Czech Republic

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