AI Article Synopsis
- CRISPR-Cas9 technology has been modified to allow precise editing of proto-oncogenes in mouse somatic tissues, overcoming previous limitations in efficiency and flexibility.
- The modifications facilitate rapid tumor formation in mammary glands, generating more consistent research models that mirror human cancer features.
- This advancement bridges the gap between innovative CRISPR methods and reliable mouse models for understanding tumor development and testing new cancer treatments.
Article Abstract
CRISPR-Cas9 has been used successfully to introduce indels in somatic cells of rodents; however, precise editing of single nucleotides has been hampered by limitations of flexibility and efficiency. Here, we report technological modifications to the CRISPR-Cas9 vector system that now allows homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic tissues to generate tumor models with high flexibility and efficiency. Somatic editing of either or in both normal and hyperplastic mammary glands led to swift tumorigenesis. The resulting tumors shared some histological, transcriptome, and proteome features with tumors induced by lentivirus-mediated expression of the respective oncogenes, but they also exhibited some distinct characteristics, particularly showing less intertumor variation, thus potentially offering more consistent models for cancer studies and therapeutic development. Therefore, this technological advance fills a critical gap between the power of CRISPR technology and high-fidelity mouse models for studying human tumor evolution and preclinical drug testing.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10181191 | PMC |
| http://dx.doi.org/10.1126/sciadv.ade0059 | DOI Listing |
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