First sickle cell patient treated with CRISPR remains crisis-free seven years later

Victoria Gray, diagnosed with sickle cell disease at three months old in Goodman, Mississippi, spent decades enduring unpredictable vaso-occlusive crises that required frequent hospitalizations, blood transfusions, and high-dose opioids. By her twenties, the pain and inconsistent adult care led her to stop planning for the future.

In 2019, after a bone marrow transplant evaluation in Nashville, her physician Haydar Frangoul offered enrollment in a clinical trial of an experimental CRISPR-Cas9 therapy, CTX001 (later approved as exagamglogene autotemcel). Gray became the first patient worldwide to receive the treatment for sickle cell disease.

The therapy uses CRISPR-Cas9 to disrupt the BCL11A erythroid enhancer in autologous CD34+ hematopoietic stem and progenitor cells, reactivating fetal hemoglobin (HbF) production to compensate for the defective adult hemoglobin. The process required mobilization and apheresis of stem cells, ex vivo editing, myeloablative busulfan conditioning, and reinfusion of the edited cells.

Since the July 2, 2019 infusion, Gray has experienced zero sickle cell crises, has not required blood transfusions, and reports sustained elevation of fetal hemoglobin levels. She has returned to full-time work, travels regularly, and participates in family activities that were previously impossible during winter months when cold triggered episodes.

The clinical trial, sponsored by Vertex Pharmaceuticals and CRISPR Therapeutics, enrolled additional patients after Gray. Interim data presented through 2023 showed that the majority of treated sickle cell participants achieved freedom from vaso-occlusive crises for at least 12 months, with durable HbF induction.

The U.S. Food and Drug Administration approved exagamglogene autotemcel for sickle cell disease in December 2023, based on trial data including Gray's outcome. The therapy carries risks including prolonged cytopenias, infections, and potential off-target editing, and requires specialized transplant centers.

Jennifer Doudna, whose UC Berkeley laboratory co-discovered CRISPR-Cas9 genome editing in 2012, noted that Gray's willingness to be the first treated patient was essential to advancing the therapy from laboratory research to clinical reality. Doudna emphasized the role of public funding in enabling the foundational science.

Gray now advocates for broader access to gene therapies, particularly in regions with high sickle cell prevalence such as sub-Saharan Africa and India, where the estimated 8 million affected individuals face limited healthcare infrastructure. Long-term follow-up of trial participants continues to monitor durability and late effects.