| First Author | Sevim-wunderlich S | Year | 2024 |
| Journal | Genes | Mgi Jnum | J:348671 |
| Mgi Id | MGI:7643493 | Doi | 10.3390/genes15060706 |
| Citation | Sevim-wunderlich S, et al. (2024) A Mouse Model of X-Linked Chronic Granulomatous Disease for the Development of CRISPR/Cas9 Gene Therapy. Genes |
| abstractText | Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease mainly caused by mutations in the X-linked CYBB gene that abrogate reactive oxygen species (ROS) produc-tion in phagocytes and microbial defense. Gene repair using the CRISPR/Cas9 system in hematopoi-etic stem and progenitor cells (HSPCs) is a promising technology for therapy for CGD. To support the establishment of efficient and safe gene therapies for CGD, we generated a mouse model harboring a patient-derived mutation in the CYBB gene. Our CybbC517del mouse line shows the hallmarks of CGD and provides a source for Cybb-deficient HSPCs that can be used to evaluate gene-therapy approaches in vitro and in vivo. In a setup using Cas9 RNPs and an AAV repair vector in HSPCs, we show that the mutation can be repaired in 19% of treated cells and that treatment restores ROS production by macrophages. In conclusion, our CybbC517del mouse line provides a new platform for refining and evaluating novel gene therapies and studying X-CGD pathophysiology. |
