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CRISPR/Cas9 在 CAR T 细胞治疗中的应用与探索。

Applications and explorations of CRISPR/Cas9 in CAR T-cell therapy.

出版信息

Brief Funct Genomics. 2020 May 20;19(3):175-182. doi: 10.1093/bfgp/elz042.

Abstract

Chimeric antigen receptor(CAR) T-cell therapy has shown remarkable effects and promising prospects in patients with refractory or relapsed malignancies, pending further progress in the next-generation CAR T cells with more optimized structure, enhanced efficacy and reduced toxicities. The clustered regulatory interspaced short palindromic repeat/CRISPR-associated protein 9 (CRISPR/Cas9) technology holds immense promise for advancing the field owing to its flexibility, simplicity, high efficiency and multiplexing in precise genome editing. Herein, we review the applications and explorations of CRISPR/Cas9 technology in constructing allogenic universal CAR T cells, disrupting inhibitory signaling to enhance potency and exploration of safer and more controllable novel CAR T cells.

摘要

嵌合抗原受体(CAR)T 细胞疗法在难治性或复发性恶性肿瘤患者中显示出显著的效果和广阔的前景,期待下一代 CAR T 细胞在结构更优化、疗效增强和毒性降低方面取得进一步进展。成簇规律间隔短回文重复/CRISPR 相关蛋白 9(CRISPR/Cas9)技术具有很大的应用潜力,可以通过精确的基因组编辑提高其灵活性、简单性、高效率和多重性,从而推动该领域的发展。本文综述了 CRISPR/Cas9 技术在构建同种异体通用 CAR T 细胞、打破抑制性信号以增强效力以及探索更安全、更可控的新型 CAR T 细胞方面的应用和探索。

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