SingleSevere inflammation and lineage skewing is associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease (single cell RNAseq)

ABSTRACT: In sickle cell disease (SCD), the β6Glu→Val substitution in the β-globin chain leads to sickle hemoglobin (HbS) polymerization and red blood cell (RBC) sickling. Transplantation of autologous, genetically modified hematopoietic stem and progenitor cells (HSPCs) represents a promising therapeutic option for patients lacking a compatible donor. We previously designed a new lentiviral vector (DREPAGLOBE LV) expressing a potent anti-sickling βAS3 globin and demonstrated its safety and efficacy in SCD patient cells (PMID: 1508458). In vitro and in vivo preclinical studies demonstrated the safety and efficacy of a gene therapy (GT) protocol based on the efficient transduction of plerixafor-mobilized SCD HSPCs by the DREPAGLOBE LV. We therefore initiated a Phase I/II open label clinical trial f

ORGANISM(S): Homo sapiens (human)

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PROVIDER: S-BSST1258 | biostudies-other |

REPOSITORIES: biostudies-other