CRISPR‐Cas9 systems: versatile cancer modelling platforms and promising therapeutic strategies

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 epigen...

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Bibliographic Details
Published in:International journal of cancer 2016-03, Vol.138 (6), p.1328-1336
Main Authors: Wen, Wan‐Shun, Yuan, Zhi‐Min, Ma, Shi‐Jie, Xu, Jiang, Yuan, Dong‐Tang
Format: Article
Language:English
Subjects:
Animals
Cancer
cancer modeling
cancer therapy
CRISPR-Cas Systems
CRISPR‐Cas9
Epigenesis, Genetic
epigenome modulation
genome editing
Genomes
Humans
Medical research
Mutation
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - therapy
RNA Editing
RNA, Guide, CRISPR-Cas Systems - genetics
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Summary: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.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.29626