IND-Enabling Studies for the Expression of Ube3a via Lentiviral Vector Delivery in Blood Cells to Treat Angelman Syndrome

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. With the promising results produced from the previously FAST-funded FT2016-001 grant, the work here aimed to move forward with IND-enabling studies.