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Transplantation of donor hematopoietic stem and progenitor cells (HSPCs) is a well-established curative treatment for various blood and immune diseases including severe combined immunodeficiency (SCID). However, it comes with significant toxicities including graft-versus-host disease (GvHD) and tissue damage resulting from use of genotoxic chemotherapy-containing conditioning regimens. Autologous transplantation using gene-modified HSPCs eliminates GvHD but currently still relies on genotoxic conditioning. Further, gene-modification of HSPCs has commonly utilized integrating viruses which carry risk of oncogenesis. The ideal therapy would eliminate the risks associated with current HSC gene-modification and conditioning approaches. Here, we combined base editors (BE), engineered virus-like particles (eVLPs) and non-genotoxic αCD117 antibody drug conjugate (ADC) conditioning to explore optimal curative treatment of SCID. We generated a Rag2 SCID mouse model with a single point mutation (pm) and corresponding BE. Rag2 HSPCs were corrected using SpCas9NG-ABE-eVLPs without off-target effects detected. Even in settings of low editing, transplantation of BE-corrected HSPCs into αCD117-ADC conditioned mice led to efficient immune cell production in peripheral blood with normal B-cell progenitors in the bone marrow. Combining αCD117-ADC conditioning with transplantation of HSPCs that were base edited using eVLPs successfully reversed the SCID phenotype in mice, showcasing a significant advancement in reducing treatment-related toxicities while enabling disease correction.