CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia
CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia
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DOI：
10.1056/nejmoa1817426
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发表时间：
2019-09-26
影响因子：
158.5
通讯作者：
Chen, Hu
中科院分区：
文献类型：
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作者：
Xu, Lei;Wang, Jun;Chen, Hu
在人类基因治疗的背景下，基于CRISPR（成簇的规则间隔短回文重复序列）的基因组编辑的安全性在很大程度上是未知的。CCR 5是治疗人类免疫缺陷病毒1型（HIV-1）感染的合理但不是绝对的保护性靶点，因为CCR 5无效的血细胞在很大程度上对HIV-1的进入具有抵抗力。我们将CRISPR编辑的CCR 5消融的造血干细胞和祖细胞（HSPC）移植到患有HIV-1感染和急性淋巴细胞白血病的患者中。急性淋巴细胞白血病完全缓解，完全供体嵌合，携带消融的CCR 5的供体细胞持续超过19个月，没有基因编辑相关的不良事件。在抗逆转录病毒治疗中断期间，CCR 5消融的CD 4+细胞百分比增加了一个小的程度。尽管我们成功移植和长期植入了CRISPR编辑的HSPC，但淋巴细胞中CCR 5破坏的百分比仅为约5%，这表明需要对这种方法进行进一步研究。（由北京市科学技术委员会等资助; ClinicalTrials.gov编号，NCT 03164135。
The safety of CRISPR (clustered regularly interspaced short palindromic repeats)-based genome editing in the context of human gene therapy is largely unknown. CCR5 is a reasonable but not absolutely protective target for a cure of human immunodeficiency virus type 1 (HIV-1) infection, because CCR5-null blood cells are largely resistant to HIV-1 entry. We transplanted CRISPR-edited CCR5-ablated hematopoietic stem and progenitor cells (HSPCs) into a patient with HIV-1 infection and acute lymphoblastic leukemia. The acute lymphoblastic leukemia was in complete remission with full donor chimerism, and donor cells carrying the ablated CCR5 persisted for more than 19 months without gene editing-related adverse events. The percentage of CD4+ cells with CCR5 ablation increased by a small degree during a period of antiretroviral-therapy interruption. Although we achieved successful transplantation and long-term engraftment of CRISPR-edited HSPCs, the percentage of CCR5 disruption in lymphocytes was only approximately 5%, which indicates the need for further research into this approach. (Funded by the Beijing Municipal Science and Technology Commission and others; ClinicalTrials.gov number, NCT03164135.)