Cellular and Molecular Therapeutics Branch, NHLBI/NIDDK, National Institutes of Health, Bethesda, MD, USA.
Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
Adv Exp Med Biol. 2019;1144:37-52. doi: 10.1007/5584_2018_331.
Sickle cell disease (SCD) is an inherited monogenic disorder resulting in serious mortality and morbidity worldwide. Although the disease was characterized more than a century ago, there are only two FDA approved medications to lessen disease severity, and a definitive cure available to all patients with SCD is lacking. Rapid and substantial progress in genome editing approaches have proven valuable as a curative option given plausibility to either correct the underlying mutation in patient-derived hematopoietic stem/progenitor cells (HSPCs), induce fetal hemoglobin expression to circumvent sickling of red blood cells (RBCs), or create corrected induced pluripotent stem cells (iPSCs) among other approaches. Recent discovery of CRISPR/Cas9 has not only revolutionized genome engineering but has also brought the possibility of translating these concepts into a clinically meaningful reality. Here we summarize genome engineering applications using CRISPR/Cas9, addressing challenges and future perspectives of CRISPR/Cas9 as a curative option for SCD.
镰状细胞病（SCD）是一种遗传性单基因疾病，在全球范围内导致严重的死亡率和发病率。尽管这种疾病在一个多世纪前就被描述过，但目前只有两种获得 FDA 批准的药物可减轻疾病的严重程度，而且所有 SCD 患者都缺乏有效的治疗方法。基因组编辑方法的快速和实质性进展已被证明是一种有价值的治疗选择，因为它有可能纠正患者来源的造血干/祖细胞（HSPCs）中的潜在突变，诱导胎儿血红蛋白表达以避免红细胞（RBCs）镰变，或创建经过校正的诱导多能干细胞（iPSCs）等方法。最近发现的 CRISPR/Cas9 不仅彻底改变了基因组工程，而且还使将这些概念转化为具有临床意义的现实成为可能。在这里，我们总结了使用 CRISPR/Cas9 的基因组工程应用，解决了 CRISPR/Cas9 作为 SCD 治疗选择的挑战和未来展望。
