Nanotechnology-leveraged CRISPR/Cas systems: icebreaking in trace cancer-related nucleic acids biosensing

As promising noninvasive biomarkers, nucleic acids provide great potential to innovate cancer early detection methods and promote subsequent diagnosis to improve the survival rates of patient. Accurate, straightforward and sensitive detection of such nucleic acid-based cancer biomarkers in complex biological samples holds significant clinical importance. However, the low abundance creates huge challenges for their routine detection. As the next-generation diagnostic tool, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) with their high programmability, sensitivity, fidelity, single-base resolution, and precise nucleic acid positioning capabilities are extremely attractive for trace nucleic acid-based cancer biomarkers (NABCBs), permitting rapid, ultra-sensitive and specific detection. More importantly, by combing with nanotechnology, it can solve the long-lasting problems of poor sensitivity, accuracy and simplicity, as well as to achieve integrated miniaturization and portable point-of-care testing (POCT) detection. However, existing literature lacks specific emphasis on this topic. Thus, we intend to propose a timely one for the readers. This review will bridge this gap by providing insights for CRISPR/Cas-based nano-biosensing development and highlighting the current state-of-art, challenges, and prospects. We expect that it can provide better understanding and valuable insights for trace NABCBs detection, thereby facilitating advancements in early cancer screening/detection/diagnostics and win practical applications in the foreseeable future.