Promising Strategies for Sickle Cell Disease and β-Thalassemia | Hematology | JAMA | JAMA Network
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Biotech Innovations
January 12, 2021

Promising Strategies for Sickle Cell Disease and β-Thalassemia

JAMA. 2021;325(2):121. doi:10.1001/jama.2020.26232

Genetic approaches against sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) increased fetal hemoglobin and appeared to improve clinical outcomes in 2 small early trials, researchers reported in the New England Journal of Medicine.

Both techniques target the BCL11A gene, which suppresses fetal hemoglobin—an important modulator of disease severity. Individuals with SCD or TDT who have a BCL11A variant that allows fetal hemoglobin to persist after infancy have little or no disease.

In 1 approach, a patient with SCD and another with TDT received a single infusion of their own CD34+ hematopoietic stem and progenitor cells edited with the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 system to reduce BCL11A protein expression and reactivate fetal hemoglobin production. In the other trial, which tested a gene therapy approach, 6 patients with severe SCD also received a single infusion of autologous CD34+ cells, but these were gene modified with a lentiviral vector encoding RNA that silences BCL11A.