Abstract：
:CRISPR/Cas9 has revolutionized cancer mouse models. Although loss-of-function genetics by CRISPR/Cas9 is well-established, generating gain-of-function alleles in somatic cancer models is still challenging because of the low efficiency of gene knock-in. Here we developed CRISPR-based Somatic Oncogene kNock-In for Cancer Modeling (CRISPR-SONIC), a method for rapid in vivo cancer modeling using homology-independent repair to integrate oncogenes at a targeted genomic locus. Using a dual guide RNA strategy, we integrated a plasmid donor in the 3'-UTR of mouse β-actin, allowing co-expression of reporter genes or oncogenes from the β-actin promoter. We showed that knock-in of oncogenic Ras and loss of p53 efficiently induced intrahepatic cholangiocarcinoma in mice. Further, our strategy can generate bioluminescent liver cancer to facilitate tumor imaging. This method simplifies in vivo gain-of-function genetics by facilitating targeted integration of oncogenes.
journal_name
Genome Medjournal_title
Genome medicineauthors
Mou H,Ozata DM,Smith JL,Sheel A,Kwan SY,Hough S,Kucukural A,Kennedy Z,Cao Y,Xue Wdoi
10.1186/s13073-019-0627-9subject
Has Abstractpub_date
2019-04-16 00:00:00pages
21issue
1issn
1756-994Xpii
10.1186/s13073-019-0627-9journal_volume
11pub_type
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