Frontiers of CRISPR-Cas9 for Cancer Research and Therapy

Abstract

In recent years, gene editing technologies have made significant progress in understanding gene function and regulation. The Clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9 (CRISPR-Cas9) system has emerged as a versatile tool for gene editing and genome engineering. In the last few years, CRISPR-Cas9 technology has been widely applied to cancer research, mainly to understand the mechanisms of oncogenesis, drug-target identification, and the development of various cell-based therapies. When combined with genome sequence information, this technology has also shown promise to cure heritable genetic disorders. This review summarizes some of the recent developments and preclinical applications of CRISPR-Cas9 technology in cancer research and therapy. We will discuss how CRISPR based approaches have been used as a tool to identify cancer-specific vulnerabilities and potential applications in cancer therapy.

Revitalizing oral cancer research: Crispr-Cas9 technology the promise of genetic editing

“…CRISPR-Cas9 technology has revolutionized cancer research and therapy by enabling the establishment of comprehensive genomic libraries for cancer patients. Studies have highlighted the potential of CRISPR-Cas9 for identifying cancer-specific vulnerabilities and drug targets ( 70 , 71 ). This is further supported by Pacini et al., who integrated large-scale CRISPR-Cas9 viability screens to identify genetic dependencies in cancer, and Michels et al., who used pooled CRISPR-Cas9 screening to identify tumor suppressors in human colon organoids ( 72 , 73 ).…”

Advancing cancer treatments: The role of oligonucleotide-based therapies in driving progress

“…The inherent DNA repair processes subsequently maintain genomic stability through two distinct pathways: an error-prone non-homologous end-joining method, which can result in deletions and insertions (indels), and a less-frequent homology-directed repair mechanism, which mends the DNA damage by incorporating external repair templates to the damaged area. 157 The sgRNA is composed of two segments: a constant sequence that creates a scaffold by several stem-loops for binding the Cas9 nuclease and an adaptable 5′ end segment of 20 nucleotides that is altered to match the target DNA sequence, allowing customization to various targets. 156 …”

“…An alternative CRISPR-Cas technique employs a modified, catalytically inactive Cas9 enzyme, known as nuclease-dead Cas9 (dCas9) to either activate or repress targeted genes. 157 dCas9 is an RNA-guided DNA binding protein generated by the inactivation of its two catalytic domains that are fused to transcription modulating domains. 158 Then, gene-specific sgRNAs guide the dCas9-transcription modulating domain complex to effector domains of specific DNA sequences to either repress (CRISPRi) or activate (CRISPRa) the transcription of target genes.…”