基因编辑在肿瘤相关动物模型构建和CART治疗中的应用  

Application of Gene Editing in the Construction of Tumor-associated Animal Models and CART Treatment

作　　者：李大力[1] 朱一凡 国昊哲 Dali Li;Yifan Zhu;Haozhe Guo(School of Life Sciences,East China Normal University,Shanghai 200241,China)

机构地区：[1]华东师范大学生命科学学院,上海200241

出　　处：《中国科学基金》2025年第1期144-152,共9页Bulletin of National Natural Science Foundation of China

基　　金：国家自然科学基金项目(32025023,32230064,32311530111)的资助。

摘　　要：基于第373期双清论坛“临床问题驱动的肿瘤研究新范式”会议内容,本文列举了基因编辑相关技术的发展历程和基本原理、肿瘤相关动物模型的构建以及基因编辑对这一领域所发挥的促进作用,并概述了其在嵌合抗原受体T细胞疗法(CART)治疗中的应用。基因编辑技术自20世纪90年代起历经多次革新,从早期的巨型核酸酶、锌指核酸酶(ZFN)和转录激活因子样效应核酸酶(TALEN),逐步发展为以CRISPR-Cas系统为核心的各类编辑工具。通过CRISPR系统可以实现自发性肿瘤动物模型的构建和肿瘤治疗靶点的筛选。另外,基因编辑技术显著推动了CART疗法的优化,通过敲除特定基因,能够增强CART疗法的安全性、有效性和通用性。综上,基因编辑技术在肿瘤模型构建及治疗领域具有广阔的应用前景。Based on the content of the 373rd Shuangqing Forum“New Paradigm of Tumor Research Driven by Clinical Problems”,this paper enumerates the development history and basic principles of gene editing technology,the techniques of constructing tumor-associated animal models,and the role of gene editing in this field,and outlines the application of tumor animal models in CART therapy.Gene editing technology has undergone multiple innovations since the 1990s,evolving from early-stage tools such as meganucleases,zinc finger nucleases(ZFN),and transcription activator-like effector nucleases(TALEN)to highly efficient systems centered on CRISPR-Cas.Through CRISPR systems,researchers can establish spontaneous tumor animal models and screen therapeutic targets for cancer.Additionally,gene editing technology has significantly advanced the optimization of CAR-T therapy.By knocking out specific genes,the safety,efficacy,and universality of CAR-T therapy have been substantially improved.In summary,gene editing technology holds broad application prospects in tumor model construction and therapeutic development.

关 键 词：基因编辑 肿瘤 动物模型 CART 

分 类 号：R73-36[医药卫生—肿瘤] Q78[医药卫生—临床医学]