Potential Curative Treatment for Alpha-Thalassemia Using CRISPR-Mediated Genome Editing

Researchers at Stanford have developed a potentially curative treatment strategy for alpha-thalassemia, one of the most common autosomal recessive disorders in the world involving the genes HBA1 and/or HBA2. The team used CRISPR-mediated genome editing to integrate a full-length alpha globin transgene at the start site of the beta globin locus in hematopoietic stem and progenitor cells (HSPCs). This work represents a novel, safe and effective approach for introducing HBA1 or HBA2 transgenes into autologous HSPCs and red blood cells in vivo or ex vivo, increasing the amount of alpha globin in red blood cells and improving the balance between alpha and beta globin. Currently, the only curative strategy for alpha-thalassemia is donor-derived hematopoietic stem cell transplantation. However, in the majority of cases no matched donor is available and even if one is identified, transplantation carries a risk of immune rejection and graft-versus-host disease. The Stanford strategy may provide a definitive cure for alpha-thalassemia by integrating into existing ex vivo HSPC editing/transduction workflows followed by autologous transplantation.

Stage of Development
Screening of clinical vectors in alpha-thalassemia patient-derived cells.