Victoria Gray, a woman from Mississippi, became the first person in the United States to receive a CRISPR gene-editing treatment for sickle cell disease when she joined a clinical trial in 2019. The impact of her treatment journey has been twofold: it showed that editing a patient’s own blood stem cells could dramatically reduce the pain crises that define severe sickle cell disease, and it helped pave the way for the first approved CRISPR-based therapy. For patients and families, her story turned gene editing from a laboratory idea into a realistic option.
Sickle Cell Disease: The Condition Behind the Story
Sickle cell disease (SCD) is an inherited blood disorder. A single change in the HBB gene, which carries the instructions for the beta chain of hemoglobin, produces an abnormal form called hemoglobin S (HbS). When oxygen levels fall, HbS molecules stick together into long rods that distort red blood cells into a rigid crescent or sickle shape.
Sickled cells are fragile and short-lived. A normal red cell survives about 120 days, while a sickled cell may last only a few weeks. This causes chronic anemia. Sickled cells also block small blood vessels, triggering vaso-occlusive crises: episodes of severe pain that can require hospital care, along with damage to organs such as the spleen, lungs, kidneys, and brain.
How it is inherited
SCD is autosomal recessive. A child is affected when they inherit a sickle gene from each parent. People who carry one copy have sickle cell trait, which usually causes no symptoms but can be passed on. When both parents carry the trait, each pregnancy has a one in four chance of a child with the disease. In the United States, SCD occurs in roughly 1 in 365 Black or African-American births.
For a deeper look at the molecular behavior of sickle hemoglobin, and how it affects the life span of sickle cell patients, see our related articles.
Victoria Gray’s Case in Context
Before her treatment, Victoria Gray lived with severe sickle cell disease, including repeated pain crises and hospital stays, an experience shared by many adults with the condition. Existing treatments had not given her lasting control, which is why she was a candidate for an experimental approach.
In 2019 she received cells edited with CRISPR-Cas9 as part of a clinical trial of the therapy then known as CTX001. In public interviews since, she has described a life no longer dominated by pain crises. Her case drew wide media attention because it offered one of the first real-world glimpses of what gene editing could do for an inherited disease.
It is worth being clear about what one person’s story can and cannot tell us. A single patient shows what is possible; the safety and effectiveness of a treatment are established by the full clinical trial and long-term follow-up of many participants.
How the Gene-Editing Treatment Works
A common misunderstanding is that the treatment “fixes” the sickle mutation. It does not. Instead, it switches back on the production of fetal hemoglobin (HbF), the form of hemoglobin we all make before birth. Fetal hemoglobin does not sickle, and people who naturally keep high HbF levels into adulthood tend to have milder disease.
After birth, a gene called BCL11A shuts down fetal hemoglobin production. The therapy uses CRISPR to disrupt a control region of BCL11A that acts in red cell precursors, so those cells resume making HbF. The treatment approved on the basis of this work is exagamglogene autotemcel (exa-cel), marketed as Casgevy.
| Step | What happens |
|---|---|
| 1. Stem cell collection | Blood stem cells are mobilized from the bone marrow and collected from the bloodstream |
| 2. Editing in the laboratory | CRISPR-Cas9 edits the BCL11A control region in the patient’s own cells |
| 3. Conditioning chemotherapy | High-dose chemotherapy (busulfan) clears the existing bone marrow to make space |
| 4. Infusion | The edited cells are returned through a vein, much like a transfusion |
| 5. Engraftment and recovery | The cells settle in the marrow and begin producing red cells rich in fetal hemoglobin; this requires a hospital stay of several weeks |
| 6. Long-term follow-up | Patients are monitored for years to track durability and late effects |
Because patients receive their own cells, there is no need to find a matched donor and no risk of graft-versus-host disease, a major complication of conventional stem cell transplants.
The Wider Impact on Sickle Cell Care
In December 2023, the US Food and Drug Administration approved exa-cel for people aged 12 and older with sickle cell disease and recurrent vaso-occlusive crises. It was the first approved therapy based on CRISPR gene editing. On the same day, a separate gene therapy, lovotibeglogene autotemcel (Lyfgenia), which uses a modified virus to add a working anti-sickling hemoglobin gene, was also approved.
These approvals changed the conversation in hematology clinics. Curative options are no longer limited to patients who happen to have a matched sibling donor. Still, gene therapy is not for everyone:
- Intensive process: conditioning chemotherapy carries real risks, including infection and infertility.
- Specialized centers: treatment is available only at a limited number of qualified hospitals.
- Cost and access: these are among the most expensive treatments in medicine, and access varies widely between countries.
- Unknowns: long-term durability and late effects are still being studied.
Standard Treatments Still Matter
Most people with SCD are managed with established treatments, and these remain essential.
| Treatment | Purpose |
|---|---|
| Hydroxyurea | Raises fetal hemoglobin and reduces pain crises and acute chest syndrome |
| Blood transfusions | Treat severe anemia and help prevent stroke in high-risk patients |
| Penicillin and vaccinations | Protect children against serious infections |
| Pain management and hydration | Control vaso-occlusive crises |
| Matched donor stem cell transplant | Established curative option when a suitable donor exists |
Early diagnosis of sickle cell disease, usually through newborn screening and confirmed with hemoglobin electrophoresis or similar testing, allows these preventive measures to start in infancy.
When to See a Doctor
Anyone with sickle cell disease should be under the regular care of a hematology team. Seek emergency care for fever of 38.3°C (101°F) or higher, chest pain or breathing difficulty, severe pain not controlled at home, sudden weakness or trouble speaking, or a painful erection lasting several hours. If you are interested in gene therapy, ask your hematologist whether you meet the eligibility criteria and for a referral to a specialist center.
Frequently Asked Questions
Is Victoria Gray cured of sickle cell disease?
She still carries the sickle cell mutation, because the treatment raises fetal hemoglobin rather than correcting the gene. However, she has publicly described being free of the severe pain crises she had before. Doctors generally describe such outcomes as a functional cure while long-term follow-up continues.
Does CRISPR therapy change the genes I pass to my children?
No. Only blood stem cells are edited, not eggs or sperm. A treated person can still pass on the sickle cell gene.
Who can get exa-cel?
In the United States, it is approved for people aged 12 and older with sickle cell disease who have recurrent vaso-occlusive crises. Eligibility also depends on overall health and the ability to tolerate conditioning chemotherapy.
Is gene therapy better than a bone marrow transplant?
Each has trade-offs. A matched sibling transplant is well established but needs a donor, while gene therapy uses your own cells but still requires intensive chemotherapy. Your hematologist can help weigh the options.
Key Takeaways
- Victoria Gray was the first US patient treated with CRISPR gene editing for sickle cell disease, in 2019.
- The therapy reactivates fetal hemoglobin rather than correcting the sickle mutation.
- Her journey helped lead to exa-cel, approved in the United States in December 2023.
- Gene therapy is intensive and not yet widely accessible, so standard care remains the foundation. Explore more in our sickle cell guide.
