美国加州大学旧金山分校科研人员使用CRISPR/Cas9 遗传修改了造血干细胞和祖细胞，从而模仿一种称为遗传性胎儿血红蛋白持续存在综合征(HPFH)的疾病，结果发现删除β珠蛋白位点的一部分，导致了得到的红细胞的γ珠蛋白基因表达高，这是遗传性胎儿血红蛋白持续存在综合征(HPFH)的一个标志;遗传性胎儿血红蛋白持续存在综合征(HPFH)和β地中海贫血或镰状细胞病双杂合的病人表现出了更温和的疾病表现，而这种模拟了遗传性胎儿血红蛋白持续存在综合征(HPFH)的方法可能为β地中海贫血或镰状细胞病病人带来一种可能的疗法。

原文链接：

genome editing using CRISPR-Cas9 to create the HPFH genotype in HSPCs: An approach for treating sickle Cell disease and β-thalassemia

原文摘要：

Hereditary persistence of fetal hemoglobin (HPFH) is a condition in some individuals who have a high level of fetal hemoglobin throughout life. Individuals with compound heterozygous β-thalassemia or sickle cell disease (SCD) and HPFH have milder clinical manifestations. Using RNA-guided clustered regularly interspaced short palindromic repeats-associated Cas9 (CRISPR-Cas9) genome-editing technology, we deleted, in normal hematopoietic stem and progenitor cells (HSPCs), 13 kb of the β-globin locus to mimic the naturally occurring Sicilian HPFH mutation. The efficiency of targeting deletion reached 31% in cells with the delivery of both upstream and downstream breakpoint guide RNA (gRNA)-guided Staphylococcus aureusCas9 nuclease (SaCas9). The erythroid colonies differentiated from HSPCs with HPFH deletion showed significantly higher γ-globin gene expression compared with the colonies without deletion. By T7 endonuclease 1 assay, we did not detect any off-target effects in the colonies with deletion. We propose that this strategy of using nonhomologous end joining (NHEJ) to modify the genome may provide an efficient approach toward the development of a safe autologous transplantation for patients with homozygous β-thalassemia and SCD.