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疾病管理中的CRISPR技术:临床转化与治疗潜力的最新综述

CRISPR Technology in Disease Management: An Updated Review of Clinical Translation and Therapeutic Potential.

作者信息

Far Bahareh Farasati, Akbari Marziyeh, Habibi Mohammad Amin, Katavand Morteza, Nasseri Sherko

机构信息

Research Laboratory of Green Organic Synthesis and Polymers, Department of Chemistry, Iran University of Science and Technology, Tehran, Iran.

Department of Genetics, Faculty of Science, Shahrekord University, Shahrekord, Iran.

出版信息

Cell Prolif. 2025 Jul 20:e70099. doi: 10.1111/cpr.70099.

Abstract

CRISPR-Cas9 technology has rapidly advanced as a transformative genome-editing platform, facilitating precise genetic modifications and expanding therapeutic opportunities across various diseases. This review explores recent developments and clinical translations of CRISPR applications in oncology, genetic and neurological disorders, infectious diseases, immunotherapy, diagnostics, and epigenome editing. CRISPR has notably progressed in oncology, where it enables the identification of novel cancer drivers, elucidation of resistance mechanisms, and improvement of immunotherapies through engineered T cells, including PD-1 knockout CAR-T cells. Clinical trials employing CRISPR-edited cells are demonstrating promising results in hematologic malignancies and solid tumours. In genetic disorders, such as hemoglobinopathies and muscular dystrophies, CRISPR-Cas9 alongside advanced editors like base and prime editors show significant potential for correcting pathogenic mutations. This potential was affirmed with the FDA's first approval of a CRISPR-based therapy, Casgevy, for sickle cell disease in 2023. Neurological disorders, including Alzheimer's, ALS, and Huntington's disease, are increasingly targeted by CRISPR approaches for disease modelling and potential therapeutic intervention. In infectious diseases, CRISPR-based diagnostics such as SHERLOCK and DETECTR provide rapid, sensitive nucleic acid detection, particularly valuable in pathogen outbreaks like SARS-CoV-2. Therapeutically, CRISPR systems target viral and bacterial genomes, offering novel treatment modalities. Additionally, CRISPR-mediated epigenome editing enables precise regulation of gene expression, expanding therapeutic possibilities. Despite these advances, significant challenges remain, including off-target effects, delivery methodologies, immune responses, and long-term genomic safety concerns. Future improvements in editor precision, innovative delivery platforms, and enhanced safety assessments will be essential to fully integrate CRISPR-based interventions into standard clinical practice, significantly advancing personalised medicine.

摘要

CRISPR-Cas9技术作为一种变革性的基因组编辑平台迅速发展,促进了精确的基因修饰,并为各种疾病拓展了治疗机会。本综述探讨了CRISPR在肿瘤学、遗传性和神经疾病、传染病、免疫治疗、诊断以及表观基因组编辑方面的最新进展和临床转化。CRISPR在肿瘤学领域取得了显著进展,它能够识别新的癌症驱动因素,阐明耐药机制,并通过工程化T细胞(包括PD-1敲除的嵌合抗原受体T细胞)改善免疫治疗。采用CRISPR编辑细胞的临床试验在血液系统恶性肿瘤和实体瘤中显示出有前景的结果。在遗传性疾病中,如血红蛋白病和肌肉萎缩症,CRISPR-Cas9与碱基编辑器和引导编辑器等先进编辑器一起,在纠正致病突变方面显示出巨大潜力。2023年美国食品药品监督管理局首次批准基于CRISPR的疗法Casgevy用于治疗镰状细胞病,证实了这种潜力。包括阿尔茨海默病、肌萎缩侧索硬化症和亨廷顿舞蹈病在内的神经疾病,越来越多地成为CRISPR方法进行疾病建模和潜在治疗干预的目标。在传染病方面,基于CRISPR的诊断方法如SHERLOCK和DETECTR提供快速、灵敏的核酸检测,在SARS-CoV-2等病原体爆发时特别有价值。在治疗上,CRISPR系统靶向病毒和细菌基因组,提供了新的治疗方式。此外,CRISPR介导的表观基因组编辑能够精确调控基因表达,拓展了治疗可能性。尽管取得了这些进展,但仍存在重大挑战,包括脱靶效应、递送方法、免疫反应以及长期基因组安全问题。未来提高编辑器的精确性、创新递送平台以及加强安全性评估对于将基于CRISPR的干预措施全面整合到标准临床实践中、显著推进个性化医疗至关重要。

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