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Review
. 2016 May 31;7(22):33461-71.
doi: 10.18632/oncotarget.8075.

Brain tumor modeling using the CRISPR/Cas9 system: state of the art and view to the future

Xiao-Yuan Mao  1   2 , Jin-Xiang Dai  3 , Hong-Hao Zhou  1   2 , Zhao-Qian Liu  1   2 , Wei-Lin Jin  4   5
Affiliations
Review

Brain tumor modeling using the CRISPR/Cas9 system: state of the art and view to the future

Xiao-Yuan Mao et al. Oncotarget. .

Abstract

Although brain tumors have been known tremendously over the past decade, there are still many problems to be solved. The etiology of brain tumors is not well understood and the treatment remains modest. There is in great need to develop a suitable brain tumor models that faithfully mirror the etiology of human brain neoplasm and subsequently get more efficient therapeutic approaches for these disorders. In this review, we described the current status of animal models of brain tumors and analyzed their advantages and disadvantages. Additionally, prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), a versatile genome editing technology for investigating the functions of target genes, and its application were also introduced in our present work. We firstly proposed that brain tumor modeling could be well established via CRISPR/Cas9 techniques. And CRISPR/Cas9-mediated brain tumor modeling was likely to be more suitable for figuring out the pathogenesis of brain tumors, as CRISPR/Cas9 platform was a simple and more efficient biological toolbox for implementing mutagenesis of oncogenes or tumor suppressors that were closely linked with brain tumors.

Keywords: CRISPR; animal models; brain tumors; oncogene; tumor suppressor.

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Conflict of interest statement

The authors declared no potential financial conflicts of interest.

Figures

Figure 1
Figure 1. The CRISPR/Cas9 system for genome engineering. The CRISPR is composed of two major components including a CRISPR-associated endonuclease (Cas9) and a single guide RNA (sgRNA)
The Cas9 from S. pyogenes (wt SpCas9) is shown in this figure as it is the most widely used in genome editing nowadays. After wt SpCas9 and sgRNA form a riboprotein complex, they can bind any genomic sequence with a protospacer adjacent motif (PAM), directing DNA double-strand breaks (DSBs) at the target site. DSBs are then repaired by either non-homologous end-joining (NHEJ) or homology-directed repair (HDR) pathway.
Figure 2
Figure 2. Proposed applications of the CRISPR/Cas9 system for brain tumor modeling
A. shows the crystal structure of wt SpCas9 referred to Zhang et al [70]; B. is the model graphs of wt SpCas9, dSpCas9, SpCas9 variants, SaCas9 and Cpf1; C. D. E. F. display the processions of four different types of CRISPR-mediated genome editing including CRISPR knock out (CRISPR KO), CRISPR knock in (CRISPR KI), CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa), respectively; G. proposes four different sorts of CRISPR/Cas9 techniques are possibly involved in brain tumor modeling (BTM). CRISPR KO is presently successfully applied for BTM (as shown by solid arrow). We propose CRISPR KI, CRISPRi and CRISPRa are used for BTM (as shown by dotted arrows).
Figure 2
Figure 2. Proposed applications of the CRISPR/Cas9 system for brain tumor modeling
A. shows the crystal structure of wt SpCas9 referred to Zhang et al [70]; B. is the model graphs of wt SpCas9, dSpCas9, SpCas9 variants, SaCas9 and Cpf1; C. D. E. F. display the processions of four different types of CRISPR-mediated genome editing including CRISPR knock out (CRISPR KO), CRISPR knock in (CRISPR KI), CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa), respectively; G. proposes four different sorts of CRISPR/Cas9 techniques are possibly involved in brain tumor modeling (BTM). CRISPR KO is presently successfully applied for BTM (as shown by solid arrow). We propose CRISPR KI, CRISPRi and CRISPRa are used for BTM (as shown by dotted arrows).
Figure 2
Figure 2. Proposed applications of the CRISPR/Cas9 system for brain tumor modeling
A. shows the crystal structure of wt SpCas9 referred to Zhang et al [70]; B. is the model graphs of wt SpCas9, dSpCas9, SpCas9 variants, SaCas9 and Cpf1; C. D. E. F. display the processions of four different types of CRISPR-mediated genome editing including CRISPR knock out (CRISPR KO), CRISPR knock in (CRISPR KI), CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa), respectively; G. proposes four different sorts of CRISPR/Cas9 techniques are possibly involved in brain tumor modeling (BTM). CRISPR KO is presently successfully applied for BTM (as shown by solid arrow). We propose CRISPR KI, CRISPRi and CRISPRa are used for BTM (as shown by dotted arrows).
Figure 2
Figure 2. Proposed applications of the CRISPR/Cas9 system for brain tumor modeling
A. shows the crystal structure of wt SpCas9 referred to Zhang et al [70]; B. is the model graphs of wt SpCas9, dSpCas9, SpCas9 variants, SaCas9 and Cpf1; C. D. E. F. display the processions of four different types of CRISPR-mediated genome editing including CRISPR knock out (CRISPR KO), CRISPR knock in (CRISPR KI), CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa), respectively; G. proposes four different sorts of CRISPR/Cas9 techniques are possibly involved in brain tumor modeling (BTM). CRISPR KO is presently successfully applied for BTM (as shown by solid arrow). We propose CRISPR KI, CRISPRi and CRISPRa are used for BTM (as shown by dotted arrows).
Figure 2
Figure 2. Proposed applications of the CRISPR/Cas9 system for brain tumor modeling
A. shows the crystal structure of wt SpCas9 referred to Zhang et al [70]; B. is the model graphs of wt SpCas9, dSpCas9, SpCas9 variants, SaCas9 and Cpf1; C. D. E. F. display the processions of four different types of CRISPR-mediated genome editing including CRISPR knock out (CRISPR KO), CRISPR knock in (CRISPR KI), CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa), respectively; G. proposes four different sorts of CRISPR/Cas9 techniques are possibly involved in brain tumor modeling (BTM). CRISPR KO is presently successfully applied for BTM (as shown by solid arrow). We propose CRISPR KI, CRISPRi and CRISPRa are used for BTM (as shown by dotted arrows).
Figure 2
Figure 2. Proposed applications of the CRISPR/Cas9 system for brain tumor modeling
A. shows the crystal structure of wt SpCas9 referred to Zhang et al [70]; B. is the model graphs of wt SpCas9, dSpCas9, SpCas9 variants, SaCas9 and Cpf1; C. D. E. F. display the processions of four different types of CRISPR-mediated genome editing including CRISPR knock out (CRISPR KO), CRISPR knock in (CRISPR KI), CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa), respectively; G. proposes four different sorts of CRISPR/Cas9 techniques are possibly involved in brain tumor modeling (BTM). CRISPR KO is presently successfully applied for BTM (as shown by solid arrow). We propose CRISPR KI, CRISPRi and CRISPRa are used for BTM (as shown by dotted arrows).
Figure 2
Figure 2. Proposed applications of the CRISPR/Cas9 system for brain tumor modeling
A. shows the crystal structure of wt SpCas9 referred to Zhang et al [70]; B. is the model graphs of wt SpCas9, dSpCas9, SpCas9 variants, SaCas9 and Cpf1; C. D. E. F. display the processions of four different types of CRISPR-mediated genome editing including CRISPR knock out (CRISPR KO), CRISPR knock in (CRISPR KI), CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa), respectively; G. proposes four different sorts of CRISPR/Cas9 techniques are possibly involved in brain tumor modeling (BTM). CRISPR KO is presently successfully applied for BTM (as shown by solid arrow). We propose CRISPR KI, CRISPRi and CRISPRa are used for BTM (as shown by dotted arrows).
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