Conclusion
This study has demonstrated the feasibility of AAV9-AIRE as a vehicle for gene therapy for APS-1.
Methods
The efficacy of AAV9-AIRE (AAV9 carrying AIRE cDNA) gene therapy was assessed in an APS-1 mouse model. We performed intrathymic injection of AAV9-AIRE into APS-1 mouse model using ultrasound imaging technique to accurately locating the thymus. We evaluated the efficiency of this approach alongside measures of autoimmunity and histology of target tissues.
Results
Intrathymic injection of AAV9-AIRE demonstrated high transduction efficiency and restored AIRE expression in the thymus. AIRE gene delivery led to a significant increase in TSA expression, and importantly a significant reduction of serum autoantibodies in treated versus control mice, which fell to near-undetectable levels by 4 weeks post-treatment. Furthermore, histological analysis of treated animals showed near-normal tissue morphology with no lymphocytic infiltrations, a hallmark of untreated Aire-deficient mice.