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CD45 epitope-edited hematopoietic stem and progenitor cells are ex vivo CRISPR adenine base–edited human CD34-positive HSPCs in which a specific amino acid substitution has been introduced into the CD45 (PTPRC) extracellular epitope to prevent recognition by CD45-targeted therapies while preserving CD45 expression and phosphatase function.[1][5][6][3] By installing a non-disruptive point mutation in the CAR/antibody epitope, these edited HSPCs engraft, persist, and reconstitute multilineage hematopoiesis in vivo, yet are resistant to cytotoxicity from CD45-directed CAR T cells, bispecific T cell engagers, and CD45-targeting antibody–drug conjugates used to selectively eradicate malignant or wild-type hematopoietic cells.[1][5][2][3] This approach, developed by academic groups at the University of Pennsylvania and collaborators and further advanced by Cimeio Therapeutics, is being positioned as a shielded stem cell platform to enable universal pan-hematologic immunotherapies and conditioning regimens for acute myeloid leukemia, B cell lymphoma, T cell leukemia, and other blood cancers, and is also being explored in multiplex editing formats (for example, with CCR5) for HIV reservoir eradication.[1][5][7]
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