美國加州大學舊金山分校科研人員使用CRISPR/Cas9 遺傳修改了造血干細胞和祖細胞，從而模仿一種稱為遺傳性胎兒血紅蛋白持續(xù)存在綜合征(HPFH)的疾病，結果發(fā)現(xiàn)刪除β珠蛋白位點的一部分，導致了得到的紅細胞的γ珠蛋白基因表達高，這是遺傳性胎兒血紅蛋白持續(xù)存在綜合征(HPFH)的一個標志;遺傳性胎兒血紅蛋白持續(xù)存在綜合征(HPFH)和β地中海貧血或鐮狀細胞病雙雜合的病人表現(xiàn)出了更溫和的疾病表現(xiàn)，而這種模擬了遺傳性胎兒血紅蛋白持續(xù)存在綜合征(HPFH)的方法可能為β地中海貧血或鐮狀細胞病病人帶來一種可能的療法。

原文鏈接：

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.