BCL-2nar4.5-edited hematopoietic stem and progenitor cells

BCL-2nar4.5-edited hematopoietic stem and progenitor cells are an investigational ex vivo gene-edited cell therapy in which autologous or donor-derived hematopoietic stem and progenitor cells (HSPCs) are modified to carry a prime-edited BCL-2 variant that confers resistance to small‑molecule BCL‑2 inhibitors, with the goal of “shielding” the hematopoietic graft during systemic BCL‑2 inhibitor treatment. Using prime editing at the BCL2 nar4.5 site, these HSPCs are engineered to preserve anti-apoptotic BCL‑2 function in the presence of BH3 mimetics such as venetoclax, enabling selective pharmacologic depletion of host or malignant cells while sparing the edited stem cell compartment.[7] This strategy is being explored preclinically as a conditioning or protection platform in hematopoietic stem cell transplantation and hematologic malignancies where BCL‑2 inhibition is used therapeutically.[7]