CRISPR-SONIC: targeted somatic oncogene knock-in enables rapid in vivo cancer modeling

Genome Med. 2019 Apr 16;11(1):21. doi: 10.1186/s13073-019-0627-9.


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.

Keywords: CRISPR; Liver cancer; Mouse model; Oncogene; RAS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Animals
  • Bile Duct Neoplasms / diagnostic imaging
  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / pathology
  • CRISPR-Cas Systems*
  • Cell Line, Tumor
  • Cholangiocarcinoma / diagnostic imaging
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / pathology
  • Gene Knock-In Techniques / methods*
  • Genes, Reporter
  • Genes, p53
  • Genes, ras*
  • Humans
  • Mice


  • Actins