Expression of Ube3a via lentiviral vector delivery in blood cells to treat Angelman syndrome

Primary Investigator: Joseph Anderson, Jill Silverman

The combination of gene therapy with hematopoietic stem cells (HSC) offers a promising approach for constitutive and life-long delivery of Ube3a to affected cells. By genetically modifying a patient’s own blood stem cells (HSCs), the modified cells can make future cells that are capable of migrating into the central nervous system (CNS) and provide a functional Ube3a copy to deficient neurons throughout the brain through a mechanism called “cross-correction.” This is a novel approach in AS in order to distribute Ube3a to more neurons of the brain than what might be achieved with traditional gene therapy using AAV. This project created a humanized mouse line to accommodate the human UBE3A gene within human blood cells, and then tested behaviors from different ages to evaluate phenotypic rescue.