Breakthrough Prize Awards $3 Million to Researchers Behind First Sickle Cell CRISPR Therapy

Dr. Swee Lay Thein of the National Heart, Lung and Blood Institute and Dr. Stuart H. Orkin of Harvard University won the 2026 Breakthrough Prize in Life Sciences worth $3 million for basic research that led to the first CRISPR-based gene therapy for sickle cell disease and beta-thalassemia. Their decades of work identified the BCL11A gene on chromosome 11 that turns off fetal hemoglobin production, which led Vertex to develop Casgevy, a treatment that uses CRISPR to edit patients' bone marrow cells to restore fetal hemoglobin production. While Casgevy represents the first functional cure for sickle cell disease, the treatment costs millions of dollars, takes up to a year, and requires harsh chemotherapy, creating barriers for the 7-8 million people globally affected by the disease, predominantly in Africa. Researchers are now developing simpler in vivo approaches that inject gene-editing machinery directly into patients and exploring drug alternatives like Mitavipat to make treatment more accessible.

Breakthrough Prize awarded for CRISPR sickle cell therapy research

• ▪Dr. Swee Lay Thein and Dr. Stuart H. Orkin received the Breakthrough Prize for basic research that led to the development of a gene therapy treating sickle cell disease and beta-thalassemia.
• ▪The Breakthrough Prize in Life Sciences has been awarded since 2013 to recognize accomplishments in the life sciences.
• ▪Dr. Stuart H. Orkin is a pediatric hematologist and oncologist at Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, and Howard Hughes Medical Institute.
• ▪Dr. Swee Lay Thein of the National Heart, Lung and Blood Institute and Dr. Stuart H. Orkin of Harvard University won the 2026 Breakthrough Prize in Life Sciences.
• ▪Dr. Swee Lay Thein is a senior investigator at the National Heart, Lung and Blood Institute.
• ▪The 2026 Breakthrough Prize in Life Sciences awarded to Dr. Swee Lay Thein and Dr. Stuart H. Orkin is worth $3 million.

Discovery of BCL11A gene's role in fetal hemoglobin production

• ▪Dr. Swee Lay Thein's team identified a region of a gene on chromosome 11 called BCL11A that affects fetal hemoglobin production.
• ▪Dr. Swee Lay Thein began her work in the 1980s trying to determine why some people with sickle cell disease and beta-thalassemia had milder forms of the diseases than others.
• ▪The BCL11A gene turns off the production of fetal hemoglobin as babies grow.
• ▪Dr. Swee Lay Thein analyzed the genes of a family of Indian origin that included more than 200 members, spanned seven generations, and lived on multiple continents.
• ▪Dr. Stuart H. Orkin showed how the BCL11A repressor mediated the switch to adult hemoglobin.
• ▪Dr. Janet Watson, a New York-based pediatrician, showed that infants who later developed sickle cell disease did not show symptoms and had red blood cells that did not sickle.
• ▪Dr. Stuart H. Orkin showed that gene editing could target the BCL11A region.
• ▪When people carry certain versions of BCL11A, the repressor does not repress and fetal hemoglobin production continues at high levels throughout life.

Casgevy treatment process and limitations

• ▪Administering Casgevy involves extracting a person's bone marrow cells, editing the BCL11A repressor using CRISPR, and then reinfusing the gene-edited bone marrow cells back into the patient.
• ▪Sickle cell disease affects around 7 million to 8 million people globally, predominantly in Africa.
• ▪Casgevy is approved to treat severe forms of beta-thalassemia.
• ▪Vertex used the CRISPR gene-editing tool to snip out the repressor region of BCL11A to develop Casgevy.

Future directions for more accessible treatments

• ▪Mitavipat is currently approved for the treatment of pyruvate kinase deficiency and beta thalassemia.
• ▪Dr. Swee Lay Thein has studied a drug called Mitavipat for treating sickle cell disease.

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