Hematopoietic stem cell genome (HSC genome) (HSC genome)

The hematopoietic stem cell (HSC) genome encompasses the entire set of genetic material within multipotent cells responsible for the lifelong production of all blood components [5]. In the context of advanced therapeutics, the HSC genome serves as a substrate for ex vivo gene therapy and gene editing to treat monogenic disorders of the blood and immune system [1, 5]. By modifying specific loci within the genome—such as the BCL11A enhancer or the HBB gene—therapeutic interventions can restore normal protein function or induce the expression of compensatory genes [1, 2]. This approach typically involves harvesting a patient's own CD34+ cells, applying genetic engineering tools like CRISPR-Cas9 or lentiviral vectors, and re-infusing the modified cells following myeloablative conditioning [3, 4]. While offering the potential for a functional cure, targeting the HSC genome necessitates careful monitoring for unintended genetic changes, such as off-target mutations or insertional mutagenesis, which could lead to clonal expansion or malignancy [2, 6].

Other names

HSC DNAHematopoietic stem cell DNAAutologous hematopoietic stem cell genomePatient HSC genome

Ex vivo genetic modification via CRISPR-Cas9 mediated gene editing or lentiviral vector-mediated gene addition to provide functional genetic sequences or disrupt regulatory elements.