CRISPR/Cas: From Tumor Gene Editing to T Cell-Based Immunotherapy of Cancer.

Mohammadreza Azangou-Khyavy,Masoud Soleimani,Mobina Ghasemi,Monire Jamalkhah,Melika Boroomand-Saboor,Javad Khanali,Jafar Kiani

doi:10.3389/fimmu.2020.02062

Abstract

The clustered regularly interspaced short palindromic repeats system has demonstrated considerable advantages over other nuclease-based genome editing tools due to its high accuracy, efficiency, and strong specificity. Given that cancer is caused by an excessive accumulation of mutations that lead to the activation of oncogenes and inactivation of tumor suppressor genes, the CRISPR/Cas9 system is a therapy of choice for tumor genome editing and treatment. In defining its superior use, we have reviewed the novel applications of the CRISPR genome editing tool in discovering, sorting, and prioritizing targets for subsequent interventions, and passing different hurdles of cancer treatment such as epigenetic alterations and drug resistance. Moreover, we have reviewed the breakthroughs precipitated by the CRISPR system in the field of cancer immunotherapy, such as identification of immune system-tumor interplay, production of universal Chimeric Antigen Receptor T cells, inhibition of immune checkpoint inhibitors, and Oncolytic Virotherapy. The existing challenges and limitations, as well as the prospects of CRISPR based systems, are also discussed.

Highlights

In recent years, various genetic manipulation techniques have been developed which involve DNA repair mechanisms that incorporate site-specific modifications into a cell’s genome
This study revealed the correlation between TIAM1 overexpression in CRC cells and cancer-associated fibroblasts with drug resistance, serving as a predictive tool, and introduced this molecule as a potential therapeutic target to reverse drug resistance [55]
Despite sublime influences given by the Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system in gene therapy, there are still many challenges that have to be considered

Summary

INTRODUCTION

Various genetic manipulation techniques have been developed which involve DNA repair mechanisms that incorporate site-specific modifications into a cell’s genome These techniques have made diverse genome alterations in a site-specific manner possible, as they are able to edit tumor cells’ genome to induce apoptosis, reduce drug resistance, and restore mutant genes. The third system, CRISPR/Cas, was first introduced by Cong et al and Mali et al as a mammalian cell genome editing platform [11,12,13] This discovery has led to dramatic improvements in genetic manipulation specificity and efficacy. The (crRNA)/Cas protein(s) complex detects mobile genetic elements with sequence specificity primarily arising from Watson-Crick base pairing between crRNA and target DNA [21].

CRISPR Versus ZFN and TALEN

CRISPR AND IMMUNOTHERAPY

Findings

DISCUSSION AND FUTURE