Engineering monocyte/macrophage-specific glucocerebrosidase expression in human hematopoietic stem cells using genome editing.

ABSTRACT: Gaucher disease is a lysosomal storage disorder caused by insufficient glucocerebrosidase activity. Its hallmark manifestations are attributed to infiltration and inflammation by macrophages. Current therapies for Gaucher disease include life-long intravenous administration of recombinant glucocerebrosidase and orally-available glucosylceramide synthase inhibitors. An alternative approach is to engineer the patient's own hematopoietic system to restore glucocerebrosidase expression, thereby replacing the affected cells, and constituting a potential one-time therapy for this disease. Here, we report an efficient CRISPR/Cas9-based approach that targets glucocerebrosidase expression cassettes with a monocyte/macrophage-specific element to the CCR5 safe-harbor locus in human hematopoietic stem

SUBMITTER: Scharenberg SG 

PROVIDER: S-EPMC7335164 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature