CRISPR-Cas9 基因编辑疗法,西非尼日利亚镰状细胞病的治愈希望

Babatunde Olowu, Ahmed Olaide, Oluwaloni Tinubu
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摘要

镰状细胞性贫血是基因突变导致的血红蛋白异常之一--它是由于遗传了两个有缺陷的基因,导致血红蛋白β链上的谷氨酸异常取代缬氨酸,从而使血红蛋白分子粘连在一起。根据世界卫生组织(WHO)的一份报告,每 1000 名新生儿中就有 20 人患有镰状细胞贫血症,而 24% 的尼日利亚人是这种突变基因的携带者。科学家们提出了几种解决方案,包括干细胞移植和基因疗法,但由于伦理观念、高昂的费用以及随之而来的免疫问题,这些方案都遭到了反对。目前的研究重点是推进基因组编辑技术,以实现基因治疗。正在进行的研究证明,通过修改基因组的特定位点,而不是在细胞中引入受影响基因的新拷贝,可以有条不紊地纠正基因差异;由于这种方法的有效性,科学家们正在测试其在各种系统中操纵基因的应用。这篇综述关联了几项使用最近开发的技术--CRISPR-Cas9--作为基因治疗新方法的研究,剖析了有关镰状细胞病因的不同临床研究,指出了它在伦理和医学方面的许多局限性、这些局限性的后果以及这项技术所带来的进步。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CRISPR-Cas9 Gene Editing Therapy, a Curative Hope for Sickle Cell in Nigeria, West Africa
Sickle cell anaemia is one of the haemoglobin abnormalities resulting from a genetic mutation— it is caused by inheriting two faulty genes that result in an abnormal substitution of glutamate for valine on the beta chain of haemoglobin, which causes haemoglobin molecules to stick together. According to a World Health Organization (WHO) report, 20 out of every 1,000 births suffer from sickle-cell anaemia, and 24% of Nigerians are carriers of this mutant gene. Scientists have suggested several solutions, including stem cell transplantation and gene therapies, but these have faced opposition due to ethical beliefs, high cost, and the ensuing immune issues. Research is now centered on advancing genome editing techniques for gene therapy. Ongoing studies have proven that genetic differences can be corrected methodically by modifying the genome at specific sites instead of introducing a new copy of the affected gene into the cells; due to the effectiveness of this method, scientists are testing its applications in manipulating genes in various systems. This review correlates a few studies that used the recently developed technique—CRISPR-Cas9—as a novel approach to gene therapy, dissecting the different clinical studies about sickle cell origin to point out many of its ethical and medical limitations, the consequences of these limitations, and the advancements this technology has made possible.
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