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中国医药导刊 ›› 2025, Vol. 27 ›› Issue (1): 101-108.

• 专栏:细胞与基因治疗 • 上一篇    

基于CRISPR的细胞产品的临床应用及监管挑战

赵宝龙, 华坚, 张长风*   

  1. 上海医药集团生物治疗技术有限公司,上海 200072
  • 收稿日期:2025-03-11 修回日期:2025-03-12 出版日期:2025-01-28 发布日期:2025-01-28

Clinical Application and Regulatory Challenges of CRISPR-Based Cell Products

  1. SPH Biotherapy.limitd Shanghai 200072, China
  • Received:2025-03-11 Revised:2025-03-12 Online:2025-01-28 Published:2025-01-28

摘要:

以嵌合抗原受体T细胞(CAR-T)为代表的免疫细胞治疗产品为多种癌症的治疗策略带来了突破性改变,但实体瘤疗效以及异体使用等问题仍阻碍细胞治疗领域的进一步发展。基因编辑技术可以通过改造免疫细胞的生物学功能来克服上述技术瓶颈。其中,规律间隔成簇短回文重复序列(CRISPR)技术由于具备成本低、准确度高等特点而成为目前最常用的基因编辑工具。因此,CRISPR也被认为是开发下一代细胞治疗产品的关键。然而,作为一种新兴技术,CRISPR会在细胞产品中诱导非预期的基因改变,并对临床应用带来潜在风险,而行业内对此类风险的了解仍非常有限。本研究结合细胞治疗领域的最新研究情况,概述CRISPR技术在细胞治疗产品中的研究进展,总结20162024年全球开展的基于CRISPR技术的细胞产品的临床试验情况,重点描述临床研究类型、基因编辑靶点、适应证种类等要素,并基于国内外政策法规与临床实践情况,分析CRISPR技术相关细胞产品的基因风险以及评估策略,以期为该类产品的临床开发和监管政策制定提供借鉴。


关键词:  , CRISPR;基因编辑;细胞治疗;药品监管;监管挑战

Abstract:

 Immune cell products particularly those involving chimeric antigen receptor T cell CAR-T therapies have emerged as revolutionary therapeutic strategies for multiple cancers. However challenges including solid tumor treatment and allogeneic use impede further advancements of cell therapy. Gene-editing technologies may overcome such challenges by reprogramming the biological functions of immune cells. Currently clustered regularly interspaced short palindromic repeats CRISPR technology is the most commonly used gene-editing tool considering its lower cost and more precise control over target genes. As such the field views CRISPR as a key to the design of next-generation cell products. Nevertheless as an emerging technology CRPSIR induces unexpected genetic changes in cell products leading to potential risks in clinical application. The fields understanding of such risks is still limited. Being combined with the latest research situation in the field of cell therapy this study summarized the research progress of CRISPR technology in cell therapy productssummarized the clinical trial situation of cell products based on CRISPR technology carried out worldwide between 2016 and 2024. The elements as the type of clinical research trial types gene targets indications etc. were described in detail.Based on domestic and foreign policies regulations and clinical practice the gene risks of CRISPR-related cell products and the evaluation strategies were analyzed so as to provide references for the clinical development and regulatory policy formulation of such products.


Key words:  , CRISPR , Genome editing , Cell therapy , Pharmaceutical supervision , Regulatory challenges

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