Gene Replacement for Sickle Cell Disease: A Case Report

The substitution of valine for glutamic acid in the β-chain of hemoglobin S (HbS) is associated with the formation of hemoglobin polymers that promote vaso-occlusion, organ infarcts, and sickle cell crises. Polymer formation is retarded by hydroxyurea, which increases fetal hemoglobin, or by replacement of hematopoietic stem cells via allogeneic transplantation. But these measures are occasionally ineffective or infeasible in many patients with sickle cell disease (SCD). Replacement of the gene for β^S-globin might cure this disorder.

To examine the safety and effectiveness of gene therapy for SCD, investigators prepared a modified β^A-globin gene encoding an antisickling variant (β^A-T87Q) incorporated into a self-inactivating lentiviral vecto…