Gene Editing For Sickle Cell Disease

Participants will receive a daily subcutaneous (under the skin) dose of motixafortide for up to 3 consecutive days to mobilize their hematopoietic stem and progenitor cells (HSPCs) into peripheral blood. Participants who cannot tolerate motixafortide may receive a daily subcutaneous dose of plerixafor as an alternative for 3-5 consecutive days. The collection of HSPCs will be done via apheresis. The collected HSPCs will be sent to a lab to genetically modify them using CRISPR/Cas9. In the lab, the researchers will take the stem cells and purify them. The stem cells will then be mixed with the CRISPR-Cas9 gRNA ribonucleoprotein (RNP) complex to change (edit) the genes in the cells and produce the new gene edited cellular product. This gene edited drug product will be frozen until ready for infusion. Once the cellular product is ready, participants will be given Busulfan (a chemotherapy medicine) intravenously (IV) for 4 days. The thawed gene product will be given IV about 48 hours after the completion of the last dose of busulfan. Participants will be followed for 3 years on this study. After the three years, participants will be followed for 12 more years on a long-term follow-up study.