Development and IND-enabling studies of a novel Cas9 genome-edited autologous CD34+ cell therapy to induce fetal hemoglobin for sickle cell disease

To determine the genome-wide spectrum and persistence of genomic rearrangements, we applied UniDirectional Targeted Sequencing (UDiTaS) in edited normal donor CD34+ HSPCs. At day 5 and 14 post-electroporation, no reproducible translocations or structural genomic re-arrangements were identified. UDiTaS assay to detect genomic translocations in edited CD34+ HSPCs at day 5 and day 14 in three normal donors (pre-GMP engineering runs, n=3) g34_bcl11a samples are treated with two gRNAs and pre-GMP samples are treated with 1 gRNA.