Post-transcriptional genetic silencing of BCL11A to treat sickle cell disease
New England Journal of Medicine — Esrick EB, Lehmann LE, Biffi A, et al. | December 09, 2020
This study was intended to evaluate the post-transcriptional genetic silencing of BCL11A for the treatment of sickle cell disease. Researchers included individuals with sickle cell disease in a single-center, open-label pilot study. Infusion of autologous CD34+ cells transduced with the BCH-BB694 lentiviral vector was the investigational therapy, which encodes a short hairpin RNA (shRNA) targeting BCL11A mRNA embedded in a microRNA (shmiR), allowing erythroid lineage-specific knockdown. Individuals were evaluated for primary endpoints of engraftment and safety and for hematologic and clinical responses to treatment. This research confirms BCL11A inhibition as an effective target for fetal hemoglobin induction and gives preliminary data that shmiR-based gene knockdown offers a favorable risk-benefit profile in sickle cell disease.