Targeting Angelman Syndrome Therapeutics to the Brain Utilizing Novel Cell Penetrating Peptides

In the last fifteen years much progress has been made in both understanding the basic genetics of AS and developing tools for treating AS. However, one area that still needs further exploration is the method of delivery for all of the therapies being developed. The brain still remains an extremely challenging organ to target for treatments. Multiple promising technologies have been successful in animal models of AS, but achieving widespread delivery of these therapeutics in a human brain remains elusive and is a major limiting factor in the effectiveness of these therapeutic approaches. The main goal of this grant is to increase delivery options for AS therapeutics by developing novel cell penetrating peptides (CPPs) from viruses that target neuronal cells. These cell penetrating peptides will act as “access codes” through the blood brain barrier allowing for delivery of potential AS therapeutics. Development of neuronal CPPs will bring the AS field closer to a mode of delivery that is minimally invasive, dosage controlled and with potentially a minimal immune response. This has the potential to benefit all modes of therapeutics in AS and also have a broad impact in the entire neurodevelopmental field.