shRNA-mediated gene therapy for the treatment of Angelman Syndrome
Angelman syndrome occurs because of a missing or malfunctioning gene called UBE3A on the maternal chromosome. Normally, UBE3A gene expression occurs only on the maternal chromosome while the paternal chromosome is silenced.
The approach in this study builds on several recent preclinical and clinical studies which demonstrated that it is possible to activate the paternal allele by inhibiting the UBE3A antisense silencer UBE3A-ATS. This approach is commonly referred to as “stop-the-stop.” In addition, this approach utilizes adeno-associated viral vector type 9 (AAV9) gene therapy which confers widespread distribution across the central nervous system.
If effective, this could yield permanent paternal UBE3A gene expression with a one-time dosing regimen. Therefore, the experiments proposed here could represent a vast improvement over existing therapeutic intervention.