Rodent Studies of Non-Snord 116 Paternal Ube3a Activation

Although there are no currently drug approved therapies that address the underlying causes of Angelman syndrome, new molecular therapies that are targeted to specific proteins, RNA, or DNA hold tremendous promise for the future. Past work demonstrated artificial transcription factors (ATFs) that could reactivate paternal Ube3a expression by silencing Ube3a-AS transcription in mouse brain and human cells. Reducing the UBE3A-AS has the collateral effect of reducing other RNAs including SNORD116 and SNORD115. Recently, four different strategies were evaluated to use ATFs to activate paternal UBE3A without affecting SNORD116 and SNORD115 in human cells. We demonstrate positive results for two of these approaches, and are now evaluating additional experiments to test these strategies in rodent models of Angelman syndrome (AS).