Progress toward the challenging goal of HDR-based gene editing for hyper-IgM syndrome

Allogeneic hematopoietic stem cell (HSC) transplantation from healthy donors has long been the standard therapy for treating monogenic inherited immunodeficiencies and blood cell disorders, such as Wiskott-Aldrich syndrome, Fanconi anemia, severe combined immunodeficiency, chronic granulomatous disease, and hyper-immunoglobulin M (hyper-IgM) syndromes.1 However, this approach is limited by the availability of donors and the risk of clinical complications, including infections, graft-versus-host disease, and engraftment failure.