Genomic DNA of patient-derived CD34+ hematopoietic stem and progenitor cells (CD34+ HSPC genomic DNA)

Genomic DNA within patient-derived CD34+ hematopoietic stem and progenitor cells (HSPCs) serves as the primary substrate for ex vivo gene therapies and gene editing interventions (Frangoul et al., 2021, NEJM). These cells are multipotent progenitors capable of giving rise to all blood cell lineages, making their genome a critical site for correcting genetic defects in diseases like sickle cell disease and beta-thalassemia (Cavazzana-Calvo et al., 2010, Nature). Therapeutic approaches involve extracting these cells from a patient, modifying specific loci within the genomic DNA—such as the BCL11A enhancer or the HBB gene—and re-infusing the modified cells (Steinberg et al., 2020, Blood). By targeting the genomic DNA of these long-lived stem cells, permanent therapeutic effects can be achieved as the modifications are passed down to all progeny cells (Naldini, 2011, Nature Reviews Genetics). However, targeting the genome carries risks of off-target mutations or unintended genomic rearrangements that require rigorous safety monitoring (Bauer et al., 2023, Nature Medicine).

Other names

CD34+ hematopoietic stem cell DNAHSPC genomeAutologous CD34+ cell DNAHematopoietic stem and progenitor cell genomic DNA

Ex vivo modification of genomic DNA via CRISPR-Cas9 mediated gene editing or lentiviral-mediated gene addition to restore or alter protein function in hematopoietic lineages.