CRISPR-based gene editing platform to treat FOXP3-mediated immune dysregulation

Stanford inventors have identified a therapeutic CRISPR-based gene editing strategy that restores expression of Forkhead Box Protien 3 (FOXP3) isoforms that are disrupted in patients with Immunedysregulation, Polyendocrinopathy, Enteropathy X-linked Syndrome (IPEX). The FOXP3 gene is required for regulatory T (Treg) cell function, immune tolerance, T cell homeostasis, and transiently affects effector T (Teff) cells. Disruption of FOXP3 expression causes the severe and early onset development of multiple autoimmune phenotypes associated with IPEX. Current treatments for IPEX include pharmacological intervention and stem cell transplantation but are limited by low efficacy and unwanted side effects, or difficulties in donor matching and availability, and host rejection. To combat these limitations, researchers in the Pediatrics department developed a gene editing approach to insert functional FOXP3 cDNA at the endogenous locus in patient-derived cells. This approach preserves the tightly choreographed regulatory mechanisms that govern appropriate FOXP3 expression, such as precise spatio-temporal patterns and alternative splicing. This genetic construct is predicted to correct over 85% of IPEX-causing mutations in patients. Overall, this therapeutic approach has potential to accomplish genetic and phenotypic correction of the FOXP3 mutations in IPEX patients through a novel CRISPR-based approach without the negative side effects associated with existing therapies.

Stage of Development
Research - in vitro