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Updated: Apr 11, 2026
A New Toolkit for Evaluating Gene Functions using Conditional Cas9 Stabilization
Published on: September 2, 2021
CRISPR-Cas9 systems: versatile cancer modelling platforms and promising therapeutic strategies
Wan-Shun Wen1, Zhi-Min Yuan2, Shi-Jie Ma3
1Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, China.
Abstract:
The RNA-guided nuclease CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) and its variants such as nickase Cas9, dead Cas9, guide RNA scaffolds and RNA-targeting Cas9 are convenient and versatile platforms for site-specific genome editing and epigenome modulation. They are easy-to-use, simple-to-design and capable of targeting multiple loci simultaneously. Given that cancer develops from cumulative genetic and epigenetic alterations, CRISPR-Cas9 and its variants (hereafter referred to as CRISPR-Cas9 systems) hold extensive application potentials in cancer modeling and therapy. To date, they have already been applied to model oncogenic mutations in cell lines (e.g., Choi and Meyerson, Nat Commun 2014;5:3728) and in adult animals (e.g., Xue et al., Nature 2014;514:380-4), as well as to combat cancer by disabling oncogenic viruses (e.g., Hu et al., Biomed Res Int 2014;2014:612823) or by manipulating cancer genome (e.g., Liu et al., Nat Commun 2014;5:5393). Given the importance of epigenome and transcriptome in tumourigenesis, manipulation of cancer epigenome and transcriptome for cancer modeling and therapy is a promising area in the future. Whereas (epi)genetic modifications of cancer microenvironment with CRISPR-Cas9 systems for therapeutic purposes represent another promising area in cancer research. Herein, we introduce the functions and mechanisms of CRISPR-Cas9 systems in genome editing and epigenome modulation, retrospect their applications in cancer modelling and therapy, discuss limitations and possible solutions and propose future directions, in hope of providing concise and enlightening information for readers interested in this area.
Insights
CRISPR-Cas9 systems offer versatile genome editing and epigenome modulation for cancer research. These tools are advancing cancer modeling and therapy by targeting genetic and epigenetic alterations.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- CRISPR-Cas9 systems, including variants like nickase Cas9 and dead Cas9, are powerful tools for precise genome editing and epigenome modulation.
- Their ease of use, design simplicity, and multiplex targeting capabilities make them highly valuable in biological research.
Purpose of the Study:
- To review the functions and mechanisms of CRISPR-Cas9 systems in genome editing and epigenome modulation.
- To retrospectively analyze the applications of CRISPR-Cas9 systems in cancer modeling and therapy.
- To discuss current limitations, potential solutions, and future directions for CRISPR-Cas9 applications in oncology.
Main Methods:
- Review of existing literature on CRISPR-Cas9 technology and its applications in cancer research.
- Analysis of studies employing CRISPR-Cas9 for modeling oncogenic mutations and manipulating cancer genomes.
- Examination of research on epigenome and transcriptome modulation using CRISPR-Cas9 for therapeutic strategies.
Main Results:
- CRISPR-Cas9 systems have been successfully utilized to model oncogenic mutations in cell lines and animals.
- Applications include disabling oncogenic viruses and manipulating cancer genomes for therapeutic purposes.
- Emerging applications focus on epigenome and transcriptome manipulation for cancer modeling and therapy, as well as modifying the cancer microenvironment.
Conclusions:
- CRISPR-Cas9 systems hold significant potential for advancing cancer modeling and therapy due to their versatility in genome and epigenome manipulation.
- Further research into epigenome and transcriptome modulation, and cancer microenvironment modification using CRISPR-Cas9, promises novel therapeutic strategies.
- Addressing limitations and exploring future directions will be crucial for fully realizing the potential of CRISPR-Cas9 in oncology.
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