Wiskott-Aldrich syndrome protein (WASP) gene locus (WAS)

The WAS gene locus encodes the Wiskott-Aldrich syndrome protein (WASP), a critical regulator of the actin cytoskeleton expressed exclusively in hematopoietic cells. WASP acts as an effector that links signaling pathways to the Arp2/3 complex, facilitating actin polymerization necessary for immune cell migration, phagocytosis, and the formation of the immunological synapse. Mutations in the WAS gene lead to Wiskott-Aldrich syndrome, a severe X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, and recurrent infections. In the context of gene therapy, the WAS gene locus in autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) is the target for genetic modification. Therapeutic approaches, such as OTL-103, utilize lentiviral vectors to introduce a functional WAS gene into the patient's own HSPCs. Once these modified cells are re-infused and engraft in the bone marrow, they give rise to a progeny of immune cells and platelets that express functional WASP, thereby restoring immune function and correcting the bleeding phenotype.

Other names

WASPIMD2THCTHC1Wiskott-Aldrich syndrome geneWAS gene

Ex vivo gene addition using a lentiviral vector to deliver a functional copy of the WAS gene into autologous CD34+ hematopoietic stem and progenitor cells, restoring expression of the Wiskott-Aldrich syndrome protein (WASP).