Restoration of the immune system with base editing and non-genotoxic conditioning in a Rag2 point-mutant mouse model
HSPCs were corrected using SpCas9NG-ABE-eVLPs without off-target effects being 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.
Authors
- Hana Willner
- Carsten T. Charlesworth (ORCID: https://orcid.org/0000-0002-8588-6204)
- Agnieszka Czechowicz (ORCID: https://orcid.org/0000-0003-2909-2669)
- Jack A. Queenan (ORCID: https://orcid.org/0000-0003-1057-3892)
- Jessie R. Davis (ORCID: https://orcid.org/0000-0002-6911-0908)
- Leah Swartzrock (ORCID: https://orcid.org/0000-0003-0584-0896)
- Morgane Denis (ORCID: https://orcid.org/0000-0002-9485-0131)
- Carla Dib (ORCID: https://orcid.org/0000-0002-7242-8327)
- Ross C. Wilson (ORCID: https://orcid.org/0000-0002-0644-5540)
- Rina J. Mepani
- Madalena Castro
- Katie Ho
- Hiromitsu Nakauchi
- David R. Liu
Institutions
- QB3 (US)
- Broad Institute (US)
- California Institute for Regenerative Medicine (US)
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Innovative Genomics Institute (US)
- University of California, Berkeley (US)
- Stanford University (US)
Publication Details
- Journal
- Molecular Therapy
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1016/j.ymthe.2026.04.010
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Howard Hughes Medical Institute
- American Society for Transplantation and Cellular Therapy
- National Institutes of Health
- School of Medicine, Stanford University