CRISPR-driven diagnostics: Molecular mechanisms, clinical efficacy and translational challenges

IF 6.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2025-09-26 DOI:10.1002/ctm2.70482

Zilong Wang, Qianqian Wang, Jiaming Zhang, Bingyu Li, Yuke Li, Zhengbo Chen, Dandan Guo, Shuying Feng

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引用次数: 0

Abstract

Background

In the realm of public health, among the primary perils menacing human well-being, the issue of pathogen infection persists as a significant concern. Precise and timely diagnosis of diseases constitutes the bedrock for effective therapeutic interventions and epidemiological monitoring. Hence, it is crucial to develop quick, sensitive, and highly effective methods for identifying pathogen and their variants.

Material and methods

This article reviews the recent research progress in the CRISPR/Cas system for detecting nucleic acids, with an emphasis on CRISPR/Cas9, CRISPR/Cas12, and CRISPR/Cas13. Initially, we provided a concise overview of the nucleic acid detection mechanism utilizing the CRISPR/Cas system. Subsequently, we dissect the molecular mechanisms of CRISPR tools, compare their clinical efficacy against traditional methods, and explore frontier innovations such as amplification-free detection and AI integration.

Conclusion

Ultimately, we argue that CRISPR diagnostics must evolve beyond technical optimization to embrace ecological adaptability, ensuring that precision medicine serves as a bridge-rather than a barrier-to global health equity.

Key points

Core Mechanism: Explains the molecular basis of CRISPR-Cas (Cas9, Cas12, Cas13) for nucleic acid detection, leveraging crRNA-guided targeting and trans-cleavage activity for ultra-sensitive (aM level) and specific pathogen identification.
Superior Performance: Outperforms traditional methods in speed, sensitivity, and cost, making it ideal for point-of-care use in resource-limited settings.
Cutting-Edge Innovations: Covers key advances like amplification-free detection, portable device integration, and multiplex platforms.
Translation Challenges: Discusses hurdles in clinical adoption, including inhibitor interference in complex samples, scalability limitations, the need for multi-center clinical data, and varying regional regulations.
Future Outlook: Highlights emerging directions such as integrated “sample-to-result” systems and AI integration, while also addressing associated biosafety and ethical concerns, calling for robust regulatory frameworks.

Abstract Image

查看原文本刊更多论文

crispr驱动诊断：分子机制、临床疗效和转化挑战

在公共卫生领域，在威胁人类福祉的主要危险中，病原体感染问题仍然是一个重大关切。准确和及时的疾病诊断是有效治疗干预和流行病学监测的基础。因此，开发快速、灵敏、高效的病原菌及其变异鉴定方法至关重要。材料与方法本文综述了近年来CRISPR/Cas系统检测核酸的研究进展，重点介绍了CRISPR/Cas9、CRISPR/Cas12和CRISPR/Cas13。首先，我们简要概述了利用CRISPR/Cas系统的核酸检测机制。随后，我们剖析了CRISPR工具的分子机制，比较了它们与传统方法的临床疗效，并探索了无扩增检测和人工智能集成等前沿创新。最后，我们认为，CRISPR诊断必须超越技术优化，融入生态适应性，确保精准医疗成为实现全球卫生公平的桥梁，而不是障碍。核心机制：解释CRISPR-Cas （Cas9、Cas12、Cas13）进行核酸检测的分子基础，利用crrna引导的靶向和反式切割活性进行超灵敏（aM水平）和特异性病原体鉴定。优越的性能：在速度、灵敏度和成本方面优于传统方法，使其成为资源有限环境下护理点使用的理想选择。前沿创新：涵盖关键的进步，如无放大检测，便携式设备集成和多路平台。翻译挑战：讨论临床应用的障碍，包括抑制剂对复杂样本的干扰，可扩展性限制，对多中心临床数据的需求，以及不同的地区法规。未来展望：强调新兴方向，如集成的“样品到结果”系统和人工智能集成，同时也解决相关的生物安全和伦理问题，呼吁建立强有力的监管框架。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.