# CRISPR-based diagnostics for infectious diseases: mechanisms, advancements and clinical transformation prospects

## TL;DR

CRISPR-based tools like SHERLOCK and DETECTR offer highly sensitive and specific diagnostics for infectious diseases, with potential for field deployment.

## Contribution

This review systematically examines CRISPR diagnostic mechanisms and evaluates their clinical transformation prospects.

## Key findings

- CRISPR diagnostics use Cas enzymes to detect pathogen nucleic acids with high sensitivity and specificity.
- Platforms like SHERLOCK and DETECTR enable field-deployable detection of viruses, bacteria, and fungi.
- Current barriers include implementation challenges, but future pathways for clinical translation are promising.

## Abstract

Infectious diseases continue to pose significant global public health challenges, necessitating the development of rapid, sensitive, specific, and field-deployable diagnostic platforms. The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated proteins (Cas) has revolutionized genome editing and concurrently enabled a new generation of molecular diagnostic tools. Leveraging the inherent trans-cleavage activities of Cas enzymes, platforms such as SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) and DETECTR (DNA Endonuclease-Targeted CRISPR Trans Reporter) have emerged, combining target recognition precision with reporter systems to achieve ultra-sensitive detection of pathogen-specific nucleic acids. This review systematically examines the mechanistic foundations of CRISPR diagnostics, synthesizes recent advancements in infectious disease applications, evaluates their advantages in sensitivity, specificity, operational simplicity, and multiplexing capacity, and critically analyzes current implementation barriers and future translational pathways.

Diagram summarizing CRISPR-Cas diagnostic technologies, showing Cas12, Cas13, Cas9, and Cas14 protein mechanisms; platforms including SHERLOCK, DETECTR, and HOLMES; signal readouts via fluorescence, lateral flow assays, and electrochemistry; and applications in detecting viruses, bacteria, and fungi.