Genetic diseases of blood cells are prime candidates for treatment through ex vivo genome editing of hematopoietic stem/progenitor cells (HSPCs). We are working to better understand and develop therapeutic approaches for treating blood disorders like sickle cell disease, beta thalassemia, and Fanconi anemia. Sickle cell disease (SCD) is a recessive genetic disorder caused by a single mutation in the β-globin gene (HBB). Sickle hemoglobin damages red blood cells and distorts them into a “sickle” shape, which leads to painful circulatory blockages, progressive organ damage, and premature death.
We are developing genome editing into a viable therapy for sickle cell patients. We employ a ribonucleoprotein (RNP) complex consisting of Cas9 protein and single guide RNA (sgRNA), together with a single-stranded DNA oligonucleotide donor (ssODN), to enable efficient replacement of the SCD mutation in human HSPCs. We have already achieved successful editing in patient HSPCs, demonstrated safety and efficacy in a mouse model, and are now working towards a human clinical trial.