| Autor: |
Moran, Kevin, Ling, Hui, Lessard, Samuel, Vieira, Benjamin, Hong, Vu, Holmes, Michael C., Reik, Andreas, Dang, Denny, Gray, David, Levasseur, Dana, Rimmele, Pauline |
| Zdroj: |
Blood; November 2018, Vol. 132 Issue: 1, Number 1 Supplement 1 p2190-2190, 1p |
| Abstrakt: |
Increases in fetal hemoglobin (HbF) are associated with improved clinical outcomes in the inherited hemoglobinopathies. We are developing a novel gene-edited cell therapy to treat patients with sickle cell disease (SCD) and beta-thalassemia (BT) using autologous hematopoietic stem and progenitor cells (HSPCs) genetically modified with zinc finger nucleases (ZFNs) to restore high levels of HbF expression. The ZFNs have been designed to specifically target the GATA motif within an intronic erythroid-specific enhancer (ESE) of BCL11A, the gene encoding a transcriptional regulator of the fetal-to-adult hemoglobin switch. Previously, we reported successful ZFN-mediated, ex vivoBCL11Agene editing in dual mobilized HSPCs, i.e. peripheral stem cells mobilized with a combination of granulocyte colony-stimulating factor (G-CSF) and plerixafor1. The editing procedure was optimized for high on-target/low off-target modification levels and increases in HbF in erythroid progeny. This drug product, ST-400, passed extensive safety testing and is currently in a phase 1/2a clinical trial for transfusion-dependent beta-thalassemia (ClinicalTrials.gov number NCT03432364). |
| Databáze: |
Supplemental Index |
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