Prokaryotic Argonautes as programmable tools for foodborne biological hazards detection: mechanisms, applications, and prospects

Foodborne biological hazards pose notorious threats to public health and economic development by causing widespread foodborne illnesses. The development of rapid and highly sensitive detection platforms is essential for safeguarding human health and ensuring societal stability. Prokaryotic Argonaute proteins (pAgos), recognized as a new generation of programmable nucleases, have emerged as promising tools in biosensing due to their precise targeting capability and design flexibility. In this review, we systematically summarize the key milestones in the evolution of pAgos research, providing a detailed introduction of their classification, structural diversity, and functional mechanisms. Through comparison with CRISPR systems, the advantages of pAgos are highlighted and discussed. We further present a comprehensive overview of pAgo-based detection platforms applied to foodborne biological hazards, including pathogenic bacteria, mycotoxins, viruses and biomarkers, evaluating the importance and benefits of these platforms. Furthermore, we analyze current challenges and future directions for advancing pAgos technologies, offering perspectives to guide further technological breakthroughs. Based on extensive evidence, this review emphasizes the transformative potential of pAgos in nucleic acid detection, with the aim of inspiring researchers to develop innovative platforms that advance food safety monitoring.