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CRISPR/CAS9 基因组修饰在基于 T 细胞的癌症免疫治疗中的治疗潜力

英文原题:Therapeutic potential of CRISPR/CAS9 genome modification in T cell-based immunotherapy of cancer.

查看英文原题

Therapeutic potential of CRISPR/CAS9 genome modification in T cell-based immunotherapy of cancer.

PubMed 2024/02/23(内容时间) Cytotherapy Q1 · IF 4.5(JCR 2025)

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中文摘要

如今,锌指核酸酶(ZFNs)、转录激活样效应核酸酶(TALENs)和成簇规律间隔短回文重复序列(CRISPR)等基因组编辑技术正被用于临床试验以及获得性免疫缺陷综合征(AIDS)和癌症等疾病的治疗。CRISPR因其简便性和成本效益而成为最先进的基因组编辑工具之一。它能够选择性地修饰基因组中的特定位置,为治疗人类疾病提供了新的可能性。CRISPR系统利用核糖核酸-脱氧核糖核酸(RNA-DNA)识别来对抗感染、调控基因表达和治疗癌症。嵌合抗原受体(CAR)T细胞疗法利用T淋巴细胞消灭癌细胞,可通过与CRISPR技术结合加以改进。然而,使用CAR-T 细胞面临诸多挑战,包括数量和质量不足、耗竭、神经毒性、细胞因子释放综合征(CRS)、B细胞发育不全、肿瘤溶解综合征和过敏反应。关于CRISPR编辑的CAR-T 细胞的临床前研究显示出令人鼓舞的结果,靶向有害的调控基因有望在未来增强癌症治疗效果。

展开英文摘要原文

Today, genome editing technologies like zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR) are being used in clinical trials and the treatment of diseases like acquired immunodeficiency syndrome (AIDS) and cancer. CRISPR stands out as one of the most advanced tools for genome editing due to its simplicity and cost-effectiveness.

It can selectively modify specific locations in the genome, offering new possibilities for treating human diseases. The CRISPR system uses ribonucleic acid-deoxyribonucleic acid (RNA-DNA) recognition to combat infections, regulate gene expression, and treat cancer. Chimeric antigen receptor (CAR) T-cell therapy, which uses T lymphocytes to eliminate cancer cells, can be improved by combining it with CRISPR technology.

However, there are challenges in using CAR-T cells, including a lack of quantity and quality, exhaustion, neurotoxicity, cytokine release syndrome (CRS), B cell aplasia, tumor lysis syndrome, and anaphylaxis. Preclinical studies on CRISPR-edited CAR-T cells show promising results and targeting detrimental regulatory genes can enhance cancer treatment in the future.

论文信息

作者
Kavousinia P、Ahmadi MH、Sadeghian H、Hosseini Bafghi M
第一作者单位
Department of Laboratory Sciences, Faculty of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.Iran
通讯作者单位
Department of Laboratory Sciences, Faculty of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: M_Hosseini79@yahoo.com.Iran
文献类型
综述 · 非美国政府资助研究
期刊
Cytotherapy2024 May
原文标识
PubMed 38466263 · DOI 10.1016/j.jcyt.2024.02.014