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利用 CRISPR 基因编辑技术优化 CAR-T 细胞疗法的疗效、安全性与可及性

英文原题:Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy.

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Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy.

PubMed 2024/10/25(内容时间) Leukemia Q1 · IF 8.8(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法已彻底改变癌症免疫治疗。然而,提升疗效、减少不良事件和提高治疗可及性等挑战仍然存在。成簇规律间隔短回文重复序列(CRISPR)技术能够有效实现多种功能,包括精准整合、多基因编辑和全基因组功能调控。此外,利用大规模向导RNA(gRNA)遗传扰动开展CRISPR筛选,可在无偏倚的条件下解析CAR-T 细胞抗癌效力背后的机制。若干新兴CRISPR工具具有高特异性、可控性和效率,可用于改造CAR-T 细胞及发现新靶点。本综述总结了CRISPR系统改善CAR-T 细胞治疗的潜在用途,包括优化疗效和安全性,以及开发通用型CAR-T 细胞。我们还讨论CRISPR基因编辑面临的挑战,并提出解决思路,展望CAR-T 细胞疗法的未来研究方向。

展开英文摘要原文

Chimeric Antigen Receptor (CAR)-T-cell therapy has revolutionized cancer immune therapy.

However, challenges remain including increasing efficacy, reducing adverse events and increasing accessibility. Use of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology can effectively perform various functions such as precise integration, multi-gene editing, and genome-wide functional regulation.

Additionally, CRISPR screening using large-scale guide RNA (gRNA) genetic perturbation provides an unbiased approach to understanding mechanisms underlying anti-cancer efficacy of CAR T-cells. Several emerging CRISPR tools with high specificity, controllability and efficiency are useful to modify CAR T-cells and identify new targets. In this review we summarize potential uses of the CRISPR system to improve results of CAR T-cells therapy including optimizing efficacy and safety and, developing universal CAR T-cells.

We discuss challenges facing CRISPR gene editing and propose solutions highlighting future research directions in CAR T-cell therapy.

论文信息

作者
Lei T、Wang Y、Zhang Y、Yang Y、Cao J、Huang J、Chen J、Chen H
第一作者单位
The Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510145, China.China
通讯作者单位
Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. wangliangtrhos@126.com.China
文献类型
综述 · 非美国政府资助研究
期刊
Leukemia2024 Dec
原文标识
PubMed 39455854 · DOI 10.1038/s41375-024-02444-y