Efficient and sustained FOXP3 locus editing in hematopoietic stem cells as a therapeutic approach for IPEX syndrome.

ABSTRACT: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic disorder caused by mutations in the FOXP3 gene, required for generation of regulatory T (T_reg) cells. Loss of T_reg cells leads to immune dysregulation characterized by multi-organ autoimmunity and early mortality. Hematopoietic stem cell (HSC) transplantation can be curative, but success is limited by autoimmune complications, donor availability and/or graft-vs.-host disease. Correction of FOXP3 in autologous HSC utilizing a homology-directed repair (HDR)-based platform may provide a safer alternative therapy. Here, we demonstrate efficient editing of FOXP3 utilizing co-delivery of Cas9 ribonucleoprotein complexes and adeno-associated viral vectors to achieve H

SUBMITTER: Singh S 

PROVIDER: S-EPMC10818254 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature