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CRISPR/Cas:从肿瘤基因编辑到基于T细胞的癌症免疫疗法

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

作者信息

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

机构信息

Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.

出版信息

Front Immunol. 2020 Sep 29;11:2062. doi: 10.3389/fimmu.2020.02062. eCollection 2020.

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.

摘要

成簇规律间隔短回文重复序列(CRISPR)系统因其高准确性、高效性和强特异性,已证明比其他基于核酸酶的基因组编辑工具具有显著优势。鉴于癌症是由导致癌基因激活和肿瘤抑制基因失活的突变过度积累引起的,CRISPR/Cas9系统是肿瘤基因组编辑和治疗的首选疗法。在确定其卓越用途时,我们回顾了CRISPR基因组编辑工具在发现、分类和确定后续干预靶点以及克服癌症治疗的不同障碍(如表观遗传改变和耐药性)方面的新应用。此外,我们还回顾了CRISPR系统在癌症免疫治疗领域所带来的突破,如识别免疫系统与肿瘤的相互作用、生产通用嵌合抗原受体T细胞、抑制免疫检查点抑制剂以及溶瘤病毒疗法。还讨论了基于CRISPR系统的现有挑战和局限性以及前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90b7/7553049/0cb5ad0adee7/fimmu-11-02062-g001.jpg

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