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CRAFT CAR T-cells (CD3-Retained, Allogeneically Functioning T-cells) are an experimental allogeneic CAR T-cell platform developed by researchers at the Mayo Clinic. This technology utilizes CRISPR/Cas12a (specifically the AsCas12a Ultra enzyme) to target the T-cell receptor beta constant (TRBC) gene, inducing site-specific editing via the microhomology-mediated end joining (MMEJ) repair pathway. A distinguishing feature of CRAFT cells is their ability to retain CD3 expression despite the disruption of the T-cell receptor (TCR), which prevents graft-versus-host disease (GvHD) while allowing the cells to remain responsive to bispecific T-cell engagers (BiTEs). Preclinical studies have demonstrated that CRAFT CAR T-cells targeting CD19 or BAFF-R exhibit robust cytotoxicity, improved persistence, and a safer genomic profile compared to traditional CD3-disrupted allogeneic CAR T-cells.
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