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用于T细胞的CRISPR工具:靶向基因组、表观基因组和转录组。

CRISPR tools for T cells: targeting the genome, epigenome, and transcriptome.

作者信息

Wachsmann Tassilo L A, Qi Lei S

机构信息

Department of Bioengineering, Stanford University, Stanford, CA, USA.

Department of Bioengineering, Stanford University, Stanford, CA, USA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA; Chan Zuckerberg Biohub - San Francisco, San Francisco, CA, USA.

出版信息

Trends Cancer. 2025 Aug 28. doi: 10.1016/j.trecan.2025.08.001.

Abstract

T cell therapy has curative potential for many cancers. Despite impressive clinical efficacy in hematological malignancies, current T cell therapy still faces challenges related to sustaining responses, antigen escape, cytotoxicity, limited accessibility, and difficulties in treating solid tumors. The advent of CRISPR (clustered regularly interspaced short palindromic repeats) technologies provides a promising solution to these challenges. CRISPR technologies have grown from merely tools for gene knockout to sophisticated tools that can engineer cells at various levels of the genome, epigenome, and transcriptome. In this review we discuss recent technological advancements and how their application to T cells has the potential to steer the next generation of cellular therapy. We highlight emerging applications and current technological limitations that future tool development aims to overcome.

摘要

T细胞疗法对许多癌症具有治愈潜力。尽管在血液系统恶性肿瘤中临床疗效显著,但目前的T细胞疗法仍面临与维持反应、抗原逃逸、细胞毒性、可及性有限以及治疗实体瘤困难等相关的挑战。CRISPR(成簇规律间隔短回文重复序列)技术的出现为这些挑战提供了一个有前景的解决方案。CRISPR技术已从单纯的基因敲除工具发展成为能够在基因组、表观基因组和转录组的各个层面改造细胞的精密工具。在本综述中,我们讨论了近期的技术进展以及它们在T细胞中的应用如何有可能引领下一代细胞疗法。我们强调了新兴应用以及未来工具开发旨在克服的当前技术局限性。

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