Safety studies in human hematopoietic stems cells engineered using CRISPR/Cas9

Lysosomal enzyme deficiencies comprise a large group of genetic disorders that generally lack effective treatments. A potential treatment approach is to engineer the patient's own hematopoietic system to express high levels of the deficient enzyme, thereby correcting the biochemical defect and halting disease progression. Here, we present genotoxicity studies on an efficient ex vivo genome editing approach using CRISPR/Cas9 that targets the lysosomal enzyme iduronidase to the CCR5safe harbor locus in human CD34+ hematopoietic stem and progenitor cells.