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CRISPR/Cas 技术在肿瘤药物发现与治疗中的应用

英文原题:CRISPR/Cas technologies for cancer drug discovery and treatment.

PubMed 2025/03/24(内容时间) Trends Pharmacol Sci Q1 · IF 24(JCR 2025)

研究概要

成簇规律间隔短回文重复序列(CRISPR)工具正在革新基因型-表型关系的建立,并正在改变细胞和基因治疗。

中文摘要

成簇规律间隔短回文重复序列(CRISPR)工具正在革新基因型-表型关系研究,并推动细胞和基因疗法转型。在肿瘤学领域,CRISPR/CRISPR 相关蛋白 9(Cas9)、Cas12 和 Cas13 推动了癌症模型构建、肿瘤演化研究、癌症生长相关靶基因识别,以及化疗敏感性和耐药相关基因发现。此外,基于 CRISPR/Cas 的临床前治疗策略也已出现,包括生成CAR-T(CAR-T)细胞和工程化免疫细胞,以及使用精准抗癌基因编辑药物使驱动癌基因失活、抑制肿瘤支持基因,并依据遗传线路输出选择性清除癌细胞。本综述总结 CRISPR 技术对基础和应用癌症研究的整体影响,并重点介绍其临床转化所面临的希望与挑战。

展开英文摘要原文

Clustered regularly interspaced short palindromic repeats (CRISPR) tools are revolutionizing the establishment of genotype-phenotype relationships and are transforming cell- and gene-based therapies. In the field of oncology, CRISPR/CRISPR-associated protein 9 (Cas9), Cas12, and Cas13 have advanced the generation of cancer models, the study of tumor evolution, the identification of target genes involved in cancer growth, and the discovery of genes involved in chemosensitivity and resistance. Moreover, preclinical therapeutic strategies employing CRISPR/Cas have emerged. These include the generation of chimeric antigen receptor T (CAR-T) cells and engineered immune cells, and the use of precision anticancer gene-editing agents to inactivate driver oncogenes, suppress tumor support genes, and cull cancer cells in response to genetic circuit output. This review summarizes the collective impact that CRISPR technology has had on basic and applied cancer research, and highlights the promises and challenges facing its clinical translation.

论文信息

作者
Wang KC、Zheng T、Hubbard BP
第一作者单位
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada.Canada
通讯作者单位
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada. Electronic address: basil.hubbard@utoronto.ca.Canada
文献类型
综述 · 非美国政府资助研究
期刊
Trends in pharmacological sciences2025 May
原文标识
PubMed 40133194 · DOI 10.1016/j.tips.2025.02.009