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

The safety of CRISPR (clustered regularly interspaced short palindromic repeats)-based genome editing in the context of human gene therapy is largely unknown. <i>CCR5</i> is a reasonable but not absolutely protective target for a cure of human immunodeficiency virus type 1 (HIV-1) infection, because <i>CCR5</i>-null blood cells are largely resistant to HIV-1 entry. We transplanted CRISPR-edited <i>CCR5</i>-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 <i>CCR5</i> persisted for more than 19 months without gene editing-related adverse events. The percentage of CD4+ cells with <i>CCR5</i> 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 <i>CCR5</i> 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.).