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Cre-dependent Cas9-expressing pigs enable efficient in vivo genome editing
- Source :
- Genome Research, 27(12), 2061. Cold Spring Harbor Laboratory Press
- Publication Year :
- 2017
-
Abstract
- Despite being time-consuming and costly, generating genome-edited pigs holds great promise for agricultural, biomedical, and pharmaceutical applications. To further facilitate genome editing in pigs, we report here establishment of a pig line with Cre-inducible Cas9 expression that allows a variety of ex vivo genome editing in fibroblast cells including single- and multigene modifications, chromosome rearrangements, and efficient in vivo genetic modifications. As a proof of principle, we were able to simultaneously inactivate five tumor suppressor genes (TP53, PTEN, APC, BRCA1, and BRCA2) and activate one oncogene (KRAS), achieved by delivering Cre recombinase and sgRNAs, which caused rapid lung tumor development. The efficient genome editing shown here demonstrates that these pigs can serve as a powerful tool for dissecting in vivo gene functions and biological processes in a temporal manner and for streamlining the production of genome-edited pigs for disease modeling.
- Subjects :
- 0301 basic medicine
Male
Transcriptional Activation
Lung Neoplasms
Swine
Cre recombinase
Method
Computational biology
Biology
Bioinformatics
Genome
Animals, Genetically Modified
03 medical and health sciences
0302 clinical medicine
Genome editing
Bacterial Proteins
CRISPR-Associated Protein 9
Transcription Activator-Like Effector Nucleases
Genetics
Animals
Humans
Genes, Tumor Suppressor
Genetics(clinical)
Gene
Genetics (clinical)
Gene Editing
Gene Rearrangement
Transcription activator-like effector nuclease
Integrases
Cas9
Gene rearrangement
Oncogenes
Fibroblasts
Endonucleases
030104 developmental biology
030220 oncology & carcinogenesis
Swine, Miniature
Female
CRISPR-Cas Systems
Ex vivo
Subjects
Details
- Language :
- English
- ISSN :
- 10889051
- Volume :
- 27
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Genome Research
- Accession number :
- edsair.doi.dedup.....3d5fccdb3f26710dee628c733b6f345f