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• W2300360330 abstract "Abstract Mouse transgenesis has provided fundamental insights into pancreatic cancer, but is limited by the long duration of allele/model generation. Here we show transfection-based multiplexed delivery of CRISPR/Cas9 to the pancreas of adult mice, allowing simultaneous editing of multiple gene sets in individual cells. We use the method to induce pancreatic cancer and exploit CRISPR/Cas9 mutational signatures for phylogenetic tracking of metastatic disease. Our results demonstrate that CRISPR/Cas9-multiplexing enables key applications, such as combinatorial gene-network analysis, in vivo synthetic lethality screening and chromosome engineering. Negative-selection screening in the pancreas using multiplexed-CRISPR/Cas9 confirms the vulnerability of pancreatic cells to Brca2 -inactivation in a Kras -mutant context. We also demonstrate modelling of chromosomal deletions and targeted somatic engineering of inter-chromosomal translocations, offering multifaceted opportunities to study complex structural variation, a hallmark of pancreatic cancer. The low-frequency mosaic pattern of transfection-based CRISPR/Cas9 delivery faithfully recapitulates the stochastic nature of human tumorigenesis, supporting wide applicability for biological/preclinical research." @default.
• W2300360330 created "2016-06-24" @default.
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• W2300360330 date "2016-02-26" @default.
• W2300360330 modified "2023-10-16" @default.
• W2300360330 title "Multiplexed pancreatic genome engineering and cancer induction by transfection-based CRISPR/Cas9 delivery in mice" @default.
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• W2300360330 doi "https://doi.org/10.1038/ncomms10770" @default.
• W2300360330 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4773438" @default.
• W2300360330 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26916719" @default.
• W2300360330 hasPublicationYear "2016" @default.
• W2300360330 type Work @default.

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