Gene Editing-Based Technologies for Beta-Hemoglobinopathies Treatment Publisher



Rahimmanesh I¹ ; Boshtam M² ; Kouhpayeh S³ ; Khanahmad H⁴ ; Dabiri A¹ ; Ahangarzadeh S⁵ ; Esmaeili Y⁶ ; Bidram E^{6, 7} ; Vaseghi G² ; Javanmard SH¹ ; Shariati L^{7, 8} ; Zarrabi A⁹ ; Varma RS¹⁰ Show Affiliations
Source: Biology Published:2022

Abstract

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. have concentrated In this on review γ-or article, β-globin we addition, present regulating a systematic the transcription overview of factors the appliances involved in of expression of endogenous γ-globin such as KLF1, silencing of γ-globin inhibitors including BCL11A, gene editing tools for β-thalassemia treatment and paving the way for patients’ therapy. SOX6, and LRF/ZBTB7A, and gene repair strategies. In this review article, we present a systematic. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.