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. 2024 May 22;630(8017):728–735. doi: 10.1038/s41586-024-07456-3

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 7 — a, Images depicting representative mice for each tumour model (Jurkat, NALM-6, OCI-AML-2 and MOLM-14) before treatment (day 10 post tumour injection), day 14, 19 and 21 (endpoint) for each treatment arm (n = 5 mice for saline, 2 for control-SG3376 and 5 for CIM053-SG3376). b, CD45 MFI quantification of bone marrow cells of mice injected with NALM-6 cells and treated with saline, control-SG3376 or CIM053-SG3376 at endpoint. c, Experimental timeline of NBSGW mice humanised with control (sgNTC) or shielded (sg49.3) HSPCs, followed by MOLM-14 tumour xenograft injection. Mice were subjected to saline or CIM053-SG3376 treatment. Lower panels: images of representative mice before treatment (day 10 post MOLM-14 injection), day 14, 21, and at endpoint. d, Luminescence curves of individual mice. e, Survival curve from (c-d). Bone marrow (f), spleen (g) and blood (h) flow cytometry panels showing human chimerism (%BC8⁺mCD45⁻, blue gate) of mice humanised with control (sgNTC) or edited (sg49.3) HSPCs and treated with saline or CIM053-SG3376. MOLM-14 cells (BC8⁺mCherry⁺) pre-gated on human cells (%BC8⁺mCD45⁻, blue gate) are displayed by the middle panels. Edited (%BC8⁺QA17A19⁻) and unedited (%BC8⁺QA17A19⁺) cells within the non-tumour human population (%BC8⁺mCherry⁻, green gate) are shown in the bottom panels. Absolute cell counts of representative panels calculated according to input counting beads are written below each panel. i, Quantification of MOLM-14 cells (%BC8⁺mCD45⁻mCherry⁺) in bone marrow, spleen and blood. j, Quantification of non-tumour human cells (%BC8⁺mCD45^-mCherry⁻). k, Quantification of long-term haematopoietic stem cells (LT-HSC) (%BC8⁺mCD45⁻CD34⁺CD38⁻CD90⁺CD45RA⁻) in the bone marrow. (In all panels, 6-7 mice in saline groups and 8 mice in CIM053-SG3376 treated groups, plotting mean values +/− SD). (Ordinary two-way ANOVA tests (alpha 0.05) were employed to assess statistical difference between groups).

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