title: CRISPR-Cas9 systems: versatile cancer modelling platforms and promising therapeutic strategies.
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.
authors.affiliation: Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, China.
authors.forename: Wan-Shun
authors.initials: WS
authors.lastname: Wen
authors.affiliation: Cervical Disease Clinic, Jiangsu Huai'an Maternity and Children Hospital, Huai'an, China.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Yuan
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Ma
authors.affiliation: Department of Rehabilitation, the Affiliated Huai'an Hospital of Xuzhou Medical College and the Second People's Hospital of Huai'an, Huai'an, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China.
authors.forename: Dong-Tang
authors.initials: DT
authors.lastname: Yuan
mesh_terms: D000818:Animals; D064113:CRISPR-Cas Systems; D044127:Epigenesis, Genetic; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D017393:RNA Editing; D000094704:RNA, Guide, CRISPR-Cas Systems / Q000235:genetics
chemical_list: D000094704:RNA, Guide, CRISPR-Cas Systems
keywords: CRISPR-Cas9; cancer modeling; cancer therapy; epigenome modulation; genome editing