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| Item Type: | Article |
|---|---|
| Title: | A mouse model of X-linked chronic granulomatous disease for the development of CRISPR/Cas9 gene therapy |
| Creators Name: | Sevim-Wunderlich, S., Dang, T., Rossius, J., Schnütgen, F. and Kuehn, R. |
| Abstract: | 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) production in phagocytes and microbial defense. Gene repair using the CRISPR/Cas9 system in hematopoietic 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. |
| Keywords: | X-CGD, CRISPR/Cas9, Gene Therapy, Mouse Disease Model, Animals, Mice |
| Source: | Genes |
| ISSN: | 2073-4425 |
| Publisher: | MDPI |
| Volume: | 15 |
| Number: | 6 |
| Page Range: | 706 |
| Date: | June 2024 |
| Official Publication: | https://doi.org/10.3390/genes15060706 |
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