Revolutionising healing: Gene Editing's breakthrough against sickle cell disease

IF 6.9 2区 医学 Q1 HEMATOLOGY Blood Reviews Pub Date : 2024-03-07 DOI:10.1016/j.blre.2024.101185
Marija Dimitrievska , Dravie Bansal , Marta Vitale , John Strouboulis , Annarita Miccio , Kypros H. Nicolaides , Sara El Hoss , Panicos Shangaris , Joanna Jacków-Malinowska
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Abstract

Recent advancements in gene editing illuminate new potential therapeutic approaches for Sickle Cell Disease (SCD), a debilitating monogenic disorder caused by a point mutation in the β-globin gene. Despite the availability of several FDA-approved medications for symptomatic relief, allogeneic hematopoietic stem cell transplantation (HSCT) remains the sole curative option, underscoring a persistent need for novel treatments. This review delves into the growing field of gene editing, particularly the extensive research focused on curing haemoglobinopathies like SCD. We examine the use of techniques such as CRISPR-Cas9 and homology-directed repair, base editing, and prime editing to either correct the pathogenic variant into a non-pathogenic or wild-type one or augment fetal haemoglobin (HbF) production. The article elucidates ways to optimize these tools for efficacious gene editing with minimal off-target effects and offers insights into their effective delivery into cells. Furthermore, we explore clinical trials involving alternative SCD treatment strategies, such as LentiGlobin therapy and autologous HSCT, distilling the current findings. This review consolidates vital information for the clinical translation of gene editing for SCD, providing strategic insights for investigators eager to further the development of gene editing for SCD.

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彻底改变治疗:基因编辑防治镰状细胞病的突破。
镰状细胞病(Sickle Cell Disease,SCD)是一种由β-球蛋白基因点突变引起的单基因衰弱性疾病。尽管美国食品及药物管理局(FDA)批准了几种缓解症状的药物,但异体造血干细胞移植(HSCT)仍是唯一的治疗选择,这凸显了对新型治疗方法的持续需求。本综述深入探讨了不断发展的基因编辑领域,尤其是专注于治疗 SCD 等血红蛋白病的广泛研究。我们研究了 CRISPR-Cas9 和同源定向修复、碱基编辑和质粒编辑等技术的使用情况,这些技术可以将致病变体纠正为非致病或野生型变体,或增加胎儿血红蛋白 (HbF) 的生成。文章阐明了优化这些工具的方法,以实现有效的基因编辑,同时将脱靶效应降至最低,并深入探讨了如何将这些工具有效地输送到细胞中。此外,我们还探讨了涉及替代性 SCD 治疗策略的临床试验,如 LentiGlobin疗法和自体造血干细胞移植,并对目前的研究结果进行了提炼。这篇综述整合了基因编辑治疗 SCD 临床转化的重要信息,为渴望进一步发展基因编辑治疗 SCD 的研究人员提供了战略性见解。
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来源期刊
Blood Reviews
Blood Reviews 医学-血液学
CiteScore
13.80
自引率
1.40%
发文量
78
期刊介绍: Blood Reviews, a highly regarded international journal, serves as a vital information hub, offering comprehensive evaluations of clinical practices and research insights from esteemed experts. Specially commissioned, peer-reviewed articles authored by leading researchers and practitioners ensure extensive global coverage across all sub-specialties of hematology.
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