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 sickle cell disease. 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.