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CRISPR 技术:一种用于癌症建模、筛选和逆转耐药性的多功能工具。

CRISPR technology: A versatile tool to model, screen, and reverse drug resistance in cancer.

机构信息

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran.

Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran.

出版信息

Eur J Cell Biol. 2023 Jun;102(2):151299. doi: 10.1016/j.ejcb.2023.151299. Epub 2023 Feb 14.

Abstract

Drug resistance is a serious challenge in cancer treatment that can render chemotherapy a failure. Understanding the mechanisms behind drug resistance and developing novel therapeutic approaches are cardinal steps in overcoming this issue. Clustered regularly interspaced short palindrome repeats (CRISPR) gene-editing technology has proven to be a useful tool to study cancer drug resistance mechanisms and target the responsible genes. In this review, we evaluated original research studies that used the CRISPR tool in three areas related to drug resistance, namely screening resistance-related genes, generating modified models of resistant cells and animals, and removing resistance by genetic manipulation. We reported the targeted genes, study models, and drug groups in these studies. In addition to discussing different applications of CRISPR technology in cancer drug resistance, we analyzed drug resistance mechanisms and provided examples of CRISPR's role in studying them. Although CRISPR is a powerful tool for examining drug resistance and sensitizing resistant cells to chemotherapy, more studies are required to overcome its disadvantages, such as off-target effects, immunotoxicity, and inefficient delivery of CRISPR/cas9 into the cells.

摘要

耐药性是癌症治疗中的一个严重挑战,可能导致化疗失败。了解耐药性背后的机制并开发新的治疗方法是克服这一问题的关键步骤。成簇规律间隔短回文重复(CRISPR)基因编辑技术已被证明是研究癌症耐药机制和靶向相关基因的有用工具。在这篇综述中,我们评估了使用 CRISPR 工具在与耐药性相关的三个领域的原创研究,即筛选耐药相关基因、生成耐药细胞和动物的改良模型以及通过遗传操作去除耐药性。我们报告了这些研究中的靶向基因、研究模型和药物组。除了讨论 CRISPR 技术在癌症耐药性中的不同应用外,我们还分析了耐药机制,并提供了 CRISPR 在研究这些机制中的作用的实例。尽管 CRISPR 是研究耐药性和使耐药细胞对化疗敏感的强大工具,但需要更多的研究来克服其缺点,例如脱靶效应、免疫毒性和 CRISPR/cas9 向细胞内的有效传递。

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