Boston Children’s Hospital and Dana-Farber Cancer Institute researchers reported an approach aimed at reducing the toxicity of hematopoietic stem cell transplants by replacing conventional genotoxic conditioning. The strategy uses donor stem-cell epitope editing plus antibodies designed to selectively deplete patient stem cells. In Nature (“Non-genotoxic transplantation and in vivo selection through epitope editing”), the investigators demonstrated that epitope-edited donor cells could be selectively spared, while patient cells were cleared using targeting antibodies. The model seeks to preserve the ability of HSPC transplantation to rebuild the hematopoietic system without widespread DNA damage. The work is positioned as a step toward broader applicability of transplant and related gene therapy modalities that are currently constrained by conditioning-related risks, while acknowledging immune-based efficacy and safety challenges of nonselective targeting and antibody half-life.