Hydroxyurea

Erythropoietin Human Recombinant

Neridronate

Autologous human CD34+ hematopoietic stem/precursor cells (HSPCs), obtained from peripheral blood by leukapheresis from plerixaformobilized sickle cell disease (SCD) patients or granulocyte colony stimulating factor (G-CSF) and plerixafor-mobilized transfusion dependent betathalassemia (TDT) patients, genetically modified ex vivo by CRISPR/Cas12a (clustered regularly interspaced palindromic repeats/modified Acidaminococcus sp. Cas12a) endonuclease complexed with a guide RNA (gRNA) that targets the CCAAT-box region of both gamma globin gene (HBG1 and HGB2) promoters on chromosome 11, creating indels that disrupt repressor binding and increase gamma globin expression. The editing components are introduced into the target cell population as a ribonucleoprotein complex by electroporation. The cell suspension is enriched for CD34+ cells using magnetic bead separation. Following electroporation, the cells are cultured in media containing thrombopoietin, Fms-related tyrosine kinase 3 ligand (Flt3L), and stem cell factor (SCF). The substance consists of cells with ?70% CD34/CD45+ purity and ?70% on-target editing.