Recent advances in gene editing technologies using CRISPR/Cas9 allow precise genome editing at a site of interest and have accelerated human disease modeling and the development of corrective gene therapies for various genetic disorders.1,2  We adapted CRISPR/Cas9 editing of rhesus macaque (RM) hematopoietic stem and progenitor cells (HSPCs) to create the first engineered large animal model of a hematologic disease based on close phylogenetic/functional similarity of RM to human HSPCs.

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic disorder characterized by intravascular hemolysis, thrombosis, and often bone marrow failure, linked to acquired somatic loss-of-function mutations in HSPCs inactivating the X-linked PIG-A gene that encodes an enzyme necessary for cell surface expression of glycosylphophatidylinositol-anchored proteins (GPI-APs), such as CD55 and CD59.4,5  Mutant HSPCs in PNH clonally expand, often dominating erythroid, myeloid, and B-cell lineages. Several hypotheses have been proposed to...

You do not currently have access to this content.