[关键词]
[摘要]
CRISPR 等基因编辑技术在多学科、多领域产生了革命性影响,也极大地推动了肿瘤生物治疗研究方法的转变和治疗新策略的形成。在肿瘤研究中,基因编辑加速了肿瘤细胞和免疫细胞中生物治疗新靶点的发现,推动了癌基因、抑癌基因、表观分子、耐药基因等“肿瘤细胞正常化”靶向编辑新策略的提出,促进了CAR-T、TCR-T细胞等过继细胞治疗方法向“通用型”、“即用型”的迭代,也极大地加速了CAR-T 细胞等细胞治疗的临床应用。通过更加精准基因编辑系统的研发、基因递送策略的不断进步,以及多靶点编辑、定点插入和体内时空可控编辑的发展,将进一步降低基因编辑的脱靶效应,提高疗效和安全性,同时控制成本,推动基因编辑在肿瘤生物治疗中更加广泛的应用,且有望在实体瘤治疗方面实现新的突破。
[Key word]
[Abstract]
CRISPR gene editing technologies have had a revolutionary impact on many disciplines and fields, and have also greatly changed research methods of tumor biotherapy and promoted the formation of new therapeutic strategies. In tumor researches, gene editing accelerated the discovery of potential targets in biotherapeutic tumor cells and immune cells, promoted new editing strategies of "tumor cell normalization" therapy through targeting oncogene,tumor suppressor gene, epigenetic molecular, drug resistance gene etc. It also promoted the iteration of adoptive cellular therapies of CAR-T/TCR-T cells to "universal" and "off-the-shelf" therapies, and greatly accelerated the clinical application of cell therapies such as that of CAR-T cells. With the development of more accurate gene editing systems, the continuous progress of gene delivery strategies, the development of multi-target editing, site-specific insertion and in vivo spatio-temporal editing, the off-target effect of gene editing can be further reduced, the safety and accessibility improved and the cost controlled. In the future, gene editing will be more widely used in tumor biotherapy, and is expected to achieve new breakthroughs in the treatment of solid tumors.
[中图分类号]
[基金项目]
国家自然科学基金(No. 82071789,No. 82071762)