Functional restoration of immune defects in STAT1 gain-of-function disease following stem cell gene editing

The authors investigate whether gene editing can serve as a curative alternative to allogeneic hematopoietic stem cell transplantation for patients with STAT1 gain-of-function disease, which causes severe immune deficiencies. They demonstrate that adenine base editing can efficiently correct the pathogenic STAT1 mutation in patient-derived T cells and hematopoietic stem cells, restoring immune function and maintaining long-term engraftment in vivo. This study highlights the potential of gene editing to address dominant gain-of-function mutations in immunodeficiencies and other genetic disorders.