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

Haiwei Mou1, Deniz M Ozata1, Jordan L Smith1

  • 1RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, 01605, USA.

Genome Medicine
|April 17, 2019
PubMed

Insights

CRISPR-SONIC enables efficient in vivo gene knock-in for cancer modeling. This new method rapidly integrates oncogenes into mouse models, advancing cancer research and therapeutic development.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • CRISPR/Cas9 technology has transformed cancer mouse models.
  • Generating gain-of-function alleles in somatic cancer models using CRISPR/Cas9 is challenging due to low gene knock-in efficiency.

Purpose of the Study:

  • To develop a novel CRISPR-based method for efficient in vivo oncogene integration in somatic cancer models.
  • To establish a rapid and effective approach for generating gain-of-function cancer models.

Main Methods:

  • Developed CRISPR-based Somatic Oncogene kNock-In for Cancer Modeling (CRISPR-SONIC).
  • Utilized homology-independent repair for targeted oncogene integration.
  • Employed a dual guide RNA strategy to integrate a plasmid donor into the mouse β-actin 3'-UTR for co-expression.

Main Results:

  • Successfully demonstrated efficient knock-in of oncogenic Ras and p53 loss in mice.
  • Induced intrahepatic cholangiocarcinoma in mouse models.
  • Generated bioluminescent liver cancer for enhanced tumor imaging capabilities.

Conclusions:

  • CRISPR-SONIC simplifies in vivo gain-of-function genetics for cancer modeling.
  • This method facilitates targeted oncogene integration, accelerating the development of novel cancer models.
  • The strategy offers a powerful tool for studying oncogene-driven cancers and for therapeutic imaging.
Keywords:
CRISPRLiver cancerMouse modelOncogeneRAS

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