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N Engl J Med. 2019 Sep 26;381(13):1240-1247. doi: 10.1056/NEJMoa1817426. Epub 2019 Sep 11.

CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia.

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From the Department of Hematopoietic Stem Cell Transplantation (L. Xu, J.W., T.L., B.Z., L.H., H.N., Y.Z., H.C.) and the Cell and Gene Therapy Center (B.Z., L.Z., L.H., H.C.), 307 Hospital of the People's Liberation Army, the Fifth Medical Center of the People's Liberation Army General Hospital, the Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, and the Ministry of Education (MOE) Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences (Y.L., L. Xie, X.W., J.X., H.D.), and the School of Life Sciences, Center for Statistical Science and Center for Bioinformatics (L.W., C.L.), Peking University, and the Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing Key Laboratory for HIV-AIDS Research (B.S., D.M., L.L., X.L., T.Z., H.W.), Beijing, and the Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou (K.D.) - all in China.


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; number, NCT03164135.).

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