CRISPR/Cas9 Genome-Editing Technology and Potential Clinical Application in Gastric Cancer

Abstract

Gastric cancer is the subject of clinical and basic studies due to its high incidence and mortality rates worldwide. Due to the diagnosis occurring in advanced stages and the classic treatment methodologies such as gastrectomy and chemotherapy, they are extremely aggressive and limit the quality of life of these patients. CRISPR/Cas9 is a tool that allows gene editing and has been used to explore the functions of genes related to gastric cancer, in addition to being used in the treatment of this neoplasm, greatly increasing our understanding of cancer genomics. In this mini-review, we seek the current status of the CRISPR/Cas9 gene-editing technology in gastric cancer research and clinical research.

Keywords: CRISPR; gastric cancer; gene editing.

Figure 1

Timeline of CRISPR technology [16,17,18,19,21,25,26,27,28,29,30,31,32].

Figure 2

CRISPR repair mechanism. Classic CRISPR mechanism comprising the guide RNA (gRNA), target DNA, and endonuclease (Cas9), which promotes DNA cleavage by DSBs induced by Cas9. DSBs can be repaired by two main mechanisms: the NHEJ mechanism, where the ends of the strands come together (this is subject to unwanted insertions or deletions), or by the HDR pathway, which uses the recombination donor DNA templates to reconstitute the DSB.

Figure 3

Mechanisms of CRISPR, CRISPRa, and CRISPRi: (a) classic CRISPR mechanism comprising a guide RNA (gRNA), target DNA, and endonuclease (Cas9), which promotes DNA cleavage, resulting in a knockout; (b) CRISPR mechanism comprising a guide RNA (gRNA), sequence target (target DNA), and “dead” endonuclease (dCas9), without its catalytic domain, fused with inhibitory transcription factors favoring decreased expression and generating knockdown; (c) CRISPR mechanism comprising a guide RNA (gRNA), target sequence (target DNA), and “dead” endonuclease (dCas9), without its catalytic domain, fused with transcriptional activating factors, favoring increased expression and causing upregulation of a given gene.