Transforming tumor diagnostics with CRISPR/Cas

Key Points:

1. CRISPR/Cas as a Diagnostic Tool

The CRISPR/Cas system, known for gene editing, is now revolutionizing molecular diagnostics due to its high specificity and efficiency in recognizing and cleaving target sequences.

Cas9, Cas12, and Cas13 proteins enable precise detection of nucleic acids (DNA/RNA), with Cas12 and Cas13 offering additional trans-cleavage activity for signal amplification.

2. Applications in Tumor Diagnostics

Variant Gene Detection: Identifies tumor driver mutations (e.g., EGFR in lung cancer) with single-base resolution, outperforming PCR and sequencing in sensitivity and speed.

Protein Marker Detection: Uses antibody/aptamer-CRISPR hybrids to detect low-abundance proteins (e.g., VEGF, CEA) at attomolar levels, surpassing ELISA.

Liquid Biopsy: Enables ultrasensitive analysis of circulating tumor DNA (ctDNA), exosomal miRNAs, and rare circulating tumor cells (CTCs) for early cancer screening.

3. In Situ Imaging

CRISPR/Cas systems visualize tumor heterogeneity by mapping genetic mutations and RNA distributions within cells/tissues, aiding precision oncology.

4. Advantages Over Conventional Methods

Higher sensitivity/specificity: Detects rare mutations and low-abundance biomarkers.

Rapid & portable: Integrates with microfluidics, smartphones, and point-of-care devices.

Modularity: Combines with isothermal amplification, nanomaterials, and nucleic acid circuits.

5. Challenges & Future Directions

a）Reducing off-target effects and background noise.

b）Simplifying multiplex detection for clinical use.

c）Expanding applications to non-nucleic acid targets (e.g., metabolites).

Conclusion:

CRISPR/Cas-based diagnostics are poised to transform precision oncology by enabling faster, cheaper, and more accurate tumor biomarker detection—from genes to proteins to liquid biopsies.