The precision and versatility of CRISPR-based techniques, combined with the advantages of nucleic acid-based nanotechnology, hold great promise in transforming the landscape of molecular diagnostics. While significant progress has been made, current CRISPR-based platforms primarly focus on nucleic acid detection. To expand the applicability and fully leverage the advantages offered by CRISPR-based diagnostics, ongoing efforts explore molecular strategies to develop CRISPR sensors capable of detecting a diverse range of analytes beyond nucleic acids. In addition, challenges still persist in the adaptation of CRISPR platforms for point-of-care (POC) applications, involving concerns such as portability and automation, as well as the complexities associated with multiplexing. Here, we provide a detailed classification and comprehensive discussion of molecular strategies facilitating the conversion of non-nucleic acid target binding into CRISPR-powered outputs with an emphasis on their corresponding design principles. Furthermore, the second part of the review outlines current challenges and potential solutions for seamlessly integrating these strategies into user-friendly platforms and rapid tests specifically tailored for point-of-care (POC).

中文翻译：

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基于 CRISPR 的诊断应用技术的挑战和前景

基于 CRISPR 的技术的精确性和多功能性，与基于核酸的纳米技术的优势相结合，在改变分子诊断领域具有巨大的前景。虽然已经取得了重大进展，但当前基于 CRISPR 的平台主要集中在核酸检测上。为了扩大适用性并充分利用基于 CRISPR 的诊断所提供的优势，人们不断努力探索分子策略来开发能够检测核酸以外的多种分析物的 CRISPR 传感器。此外，将 CRISPR 平台应用于即时护理 (POC) 应用的挑战仍然存在，涉及可移植性和自动化以及与多重相关的复杂性等问题。在这里，我们对促进非核酸靶标结合转化为 CRISPR 输出的分子策略进行了详细的分类和全面的讨论，重点介绍了它们相应的设计原理。此外，审查的第二部分概述了当前的挑战和潜在的解决方案，以将这些策略无缝集成到用户友好的平台和专为即时护理 (POC) 定制的快速测试中。