| First Author | Hunt C | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 2770 |
| PubMed ID | 33986266 | Mgi Jnum | J:339730 |
| Mgi Id | MGI:6713861 | Doi | 10.1038/s41467-021-22932-4 |
| Citation | Hunt C, et al. (2021) Tissue-specific activation of gene expression by the Synergistic Activation Mediator (SAM) CRISPRa system in mice. Nat Commun 12(1):2770 |
| abstractText | CRISPR-based transcriptional activation is a powerful tool for functional gene interrogation; however, delivery difficulties have limited its applications in vivo. Here, we created a mouse model expressing all components of the CRISPR-Cas9 guide RNA-directed Synergistic Activation Mediator (SAM) from a single transcript that is capable of activating target genes in a tissue-specific manner. We optimized Lipid Nanoparticles and Adeno-Associated Virus guide RNA delivery approaches to achieve expression modulation of one or more genes in vivo. We utilized the SAM mouse model to generate a hypercholesteremia disease state that we could bidirectionally modulate with various guide RNAs. Additionally, we applied SAM to optimize gene expression in a humanized Transthyretin mouse model to recapitulate human expression levels. These results demonstrate that the SAM gene activation platform can facilitate in vivo research and drug discovery. |
