Development of genome editing strategies for alpha-thalassemia – GET

Alpha-thalassemia is a rare anemia with unmet clinical need, caused by reduced alpha-globin expression altering red blood cell production. The transplantation of corrected autologous hematopoietic stem cells could represent a definitive solution. Therapeutic approaches, based on gene reactivation to compensate for defective genes, have proven their efficacy in beta-hemoglobinopathies and can also benefit alpha-thalassemia. Reactivation of the alpha-globin-like zeta-globin is a promising approach as its persistent expression rescues lethality in alpha-thalassemia mice. We hypothesize that reactivating zeta-globin expression using genome editing can offer a definitive therapeutic strategy for alpha-thalassemia. We will investigate the transcriptional regulation of zeta-globin using a CRISPR-Cas9 screening and develop genome editing strategies to reactivate zeta-globin expression. Our long-term goal is to develop a universal therapeutic strategy for alpha-thalassemia increasing patient life expectancy and quality of life.