CRISPR Gene Therapy: A Promising One-Time Therapeutic Approach for Transfusion-Dependent β-Thalassemia—CRISPR-Cas9 Gene Editing for β-Thalassemia

IF 0.6 Q4 HEMATOLOGY
Udani Gamage, Kesari Warnakulasuriya, Sonali Hansika, G. Silva
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引用次数: 0

Abstract

β-Thalassemia is an inherited hematological disorder that results from genetic changes in the β-globin gene, leading to the reduced or absent synthesis of β-globin. For several decades, the only curative treatment option for β-thalassemia has been allogeneic hematopoietic cell transplantation (allo-HCT). Nonetheless, rapid progress in genome modification technologies holds great potential for treating this disease and will soon change the current standard of care for β-thalassemia. For instance, the emergence of the CRISPR/Cas9 genome editing platform has opened the door for precision gene editing and can serve as an effective molecular treatment for a multitude of genetic diseases. Investigational studies were carried out to treat β-thalassemia patients utilizing CRISPR-based CTX001 therapy targeting the fetal hemoglobin silencer BCL11A to restore γ-globin expression in place of deficient β-globin. The results of recently carried out clinical trials provide hope of CTX001 being a promising one-time therapeutic option to treat β-hemoglobinopathies. This review provides an insight into the key scientific steps that led to the development and application of novel CRISPR/Cas9–based gene therapies as a promising therapeutic platform for transfusion-dependent β-thalassemia (TDT). Despite the resulting ethical, moral, and social challenges, CRISPR provides an excellent treatment option against hemoglobin-associated genetic diseases.
CRISPR基因治疗:一种有希望的输血依赖性β-地中海贫血的一次性治疗方法- CRISPR- cas9基因编辑β-地中海贫血
β-地中海贫血是一种遗传性血液病,由β-珠蛋白基因的遗传变化引起,导致β-球蛋白的合成减少或缺失。几十年来,β-地中海贫血的唯一治疗选择是异基因造血细胞移植(allo-HCT)。尽管如此,基因组修饰技术的快速进步在治疗这种疾病方面具有巨大潜力,并将很快改变目前β-地中海贫血的护理标准。例如,CRISPR/Cas9基因组编辑平台的出现为精确基因编辑打开了大门,可以作为多种遗传疾病的有效分子治疗方法。本研究采用基于CRISPR的CTX001治疗β-地中海贫血患者,靶向胎儿血红蛋白消音器BCL11A,以恢复γ-珠蛋白表达,代替β-珠蛋白缺陷。最近进行的临床试验的结果为CTX001成为治疗β-血红蛋白病的一种有前途的一次性治疗选择提供了希望。这篇综述深入了解了导致开发和应用新型CRISPR/Cas9基因疗法的关键科学步骤,该疗法是治疗输血依赖性β-地中海贫血(TDT)的一个有前景的治疗平台。尽管由此带来了伦理、道德和社会挑战,CRISPR为对抗血红蛋白相关遗传疾病提供了一种极好的治疗选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Thalassemia Reports
Thalassemia Reports HEMATOLOGY-
自引率
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发文量
17
审稿时长
10 weeks
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