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Publication : CRISPR interference provides increased cell type-specificity compared to the Cre-loxP system.

First Author  Laster DJ Year  2023
Journal  iScience Volume  26
Issue  8 Pages  107428
PubMed ID  37575184 Mgi Jnum  J:339330
Mgi Id  MGI:7519863 Doi  10.1016/j.isci.2023.107428
Citation  Laster DJ, et al. (2023) CRISPR interference provides increased cell type-specificity compared to the Cre-loxP system. iScience 26(8):107428
abstractText  Cre-mediated recombination is frequently used for cell type-specific loss of function (LOF) studies. A major limitation of this system is recombination in unwanted cell types. CRISPR interference (CRISPRi) has been used effectively for global LOF in mice. However, cell type-specific CRISPRi, independent of recombination-based systems, has not been reported. To test the feasibility of cell type-specific CRISPRi, we produced two novel knock-in mouse models that achieve gene suppression when used together: one expressing dCas9::KRAB under the control of a cell type-specific promoter and the other expressing a single guide RNA from a safe harbor locus. We then compared the phenotypes of mice in which the same gene was targeted by either CRISPRi or the Cre-loxP system, with cell specificity conferred by Dmp1 regulatory elements in both cases. We demonstrate that CRISPRi is effective for cell type-specific LOF and that it provides improved cell type-specificity compared to the Cre-loxP system.
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