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Advances in genome editing: the technology of choice for precise and efficient β-thalassemia treatment.

Published on Apr 30, 2020in Gene Therapy3.749
· DOI :10.1038/S41434-020-0153-9
Gibran Ali (University of Health Sciences Lahore), Muhammad Akram Tariq (University of Health Sciences Lahore)+ 2 AuthorsJaved Akram10
Estimated H-index: 10
(University of Health Sciences Lahore)
Abstract
Beta (β)-thalassemia is one of the most significant hemoglobinopathy worldwide. The high prevalence of the β-thalassemia carriers aggravates the disease burden for patients and national economies in the developing world. The survival of β-thalassemia patients solely relies on repeated transfusions, which eventually results into multi-organ damage. The fetal γ-globin genes are ordinarily silenced at birth and replaced by the adult β-globin genes. However, mutations that cause lifelong persistence of fetal γ-globin, ameliorate the debilitating effects of β-globin mutations. Therefore, therapeutically reactivating the fetal γ-globin gene is a prime focus of researchers. CRISPR/Cas9 is the most common approach to correct disease causative mutations or to enhance or disrupt the expression of proteins to mitigate the effects of the disease. CRISPR/cas9 and prime gene editing to correct mutations in hematopoietic stem cells of β-thalassemia patients has been considered a novel therapeutic approach for effective hemoglobin production. However, genome-editing technologies, along with all advantages, have shown some disadvantages due to either random insertions or deletions at the target site of edition or non-specific targeting in genome. Therefore, the focus of this review is to compare pros and cons of these editing technologies and to elaborate the retrospective scope of gene therapy for β-thalassemia patients.
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References86
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Abstract The data presented in this article are related to the research article entitled as “Targeted deletion of the BCL11A gene by CRISPR-Cas9 system for fetal hemoglobin reactivation: A promising approach for gene therapy of beta-thalassemia disease " [1]. BCL11A is a master regulator of γ-globin gene silencing, and suppresses fetal hemoglobin expression by association with other γ-globin suppressors, and also interacts with human beta-globin locus control region as well as intergenic region ...
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A new class of CRISPR-based tools efficiently corrects point mutations in cell lines, animal models and perhaps the clinic. A new class of CRISPR-based tools efficiently corrects point mutations in cell lines, animal models and perhaps the clinic.
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Induction of fetal hemoglobin (HbF) via clustered regularly interspaced short palindromic repeats/Cas9–mediated disruption of DNA regulatory elements that repress γ-globin gene (HBG1 and HBG2) expression is a promising therapeutic strategy for sickle cell disease (SCD) and β-thalassemia, although the optimal technical approaches and limiting toxicities are not yet fully defined. We disrupted an HBG1/HBG2 gene promoter motif that is bound by the transcriptional repressor BCL11A. Electroporation o...
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β‐thalassaemia is a prevalent hereditary haematological disease caused by mutations in the human haemoglobin β (HBB) gene. Among them, the HBB IVS2‐654 (C > T) mutation, which is in the intron, creates an aberrant splicing site. Bone marrow transplantation for curing β‐thalassaemia is limited due to the lack of matched donors. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9), as a widely used tool for gene editing, is able to target specif...
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Beta-thalassemia and sickle cell disease (SCD) are the most prevalent monogenic diseases. These disorders are caused by quantitative or qualitative defects in the production of adult hemoglobin. Gene therapy is a potential treatment option for patients lacking an allogenic compatible hematopoietic stem cell (HSC) donor. The generation of lentiviral vectors (LVs) carrying a β-globin-like gene has revolutionized this field by allowing effective HSC transduction with no evidence of genotoxicity to ...
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: Recently, gene therapy clinical trials have been successfully applied to hemoglobinopathies, such as sickle cell disease (SCD) and β-thalassemia. Among the great discoveries that led to the design of genetic approaches to cure these disorders is the discovery of the β-globin locus control region and several associated transcription factors, which determine hemoglobin switching as well as high-level, erythroid-specific expression of genes at the s-globin locus. Moreover, increasing evidence sho...
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Allogeneic hematopoietic stem cell transplantation was until very recently, the only permanent curative option available for patients suffering from transfusion-dependent beta-thalassemia. Gene therapy, by autologous transplantation of genetically modified hematopoietic stem cells, currently represents a novel therapeutic promise, after many years of extensive preclinical research for the optimization of gene transfer protocols. Nowadays, clinical trials being held on a worldwide setting, have d...
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Abstract Background Blood transfusion-transmitted infections in individuals suffering from beta-thalassemia have been reported in Pakistan, but the information on their sociodemographic and clinical determinants is lacking. This study aims to describe the prevalence, as well as the factors, contributing in blood transfusion-transmitted infections. Method Between December 2011 and December 2013, in a non-probable sampling, 350 thalassemia patients were recruited in Lahore, Multan, Karachi and Pes...
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