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Updated: Jul 2, 2026
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A Standardized Liquid Biopsy Preanalytical Protocol for Downstream Circulating-Free DNA Applications
Published on: September 16, 2022
CRISPR-Cas12a-based liquid biopsy technology: challenges in large-scale clinical application.
Yaning Zhang1, Xiaocong Lin2, Hansen Shi2
1Department of Medical Laboratory, Affiliated Hospital of Guangdong Medical University, No. 57 South, Xiashan People's Avenue, Zhanjiang, Guangdong 524000, PR China.
Summary
CRISPR-Cas12a offers advanced detection for liquid biopsies, overcoming challenges like low target abundance. Further development is needed to address robustness and reproducibility for widespread clinical use in precision medicine.
Area of Science:
- Molecular Diagnostics
- Biotechnology
- Genomics
Background:
- Liquid biopsy enables minimally invasive detection of tumor biomarkers for cancer management.
- Current limitations include low target abundance, complex biofluid matrices, and pre-analytical variability.
- CRISPR-Cas12a presents a promising nucleic acid platform for sensitive biomarker detection.
Purpose of the Study:
- To review the mechanism and clinical potential of CRISPR-Cas12a in liquid biopsy.
- To analyze matrix-specific challenges and adaptation strategies across various biofluids.
- To identify bottlenecks and future directions for clinical translation of CRISPR-Cas12a liquid biopsy.
Main Methods:
- Review of CRISPR-Cas12a mechanism, focusing on sequence recognition and trans-cleavage amplification.
- Analysis of detection methods and performance across seven clinical biofluids (blood, urine, CSF, etc.).
- Evaluation of technical difficulties, adaptation strategies, and clinical application scenarios.
Main Results:
- CRISPR-Cas12a demonstrates significant advantages in detecting low-abundance targets in liquid biopsies.
- Matrix effects and pre-analytical variability pose challenges across different biofluids.
- Analytical sensitivity improvements alone are insufficient; robustness, reproducibility, and interpretability are key.
Conclusions:
- CRISPR-Cas12a holds substantial translational potential for liquid biopsy applications.
- Addressing detection robustness, reproducibility, and clinical interpretability is crucial for widespread adoption.
- This review provides a reference for advancing CRISPR-Cas12a liquid biopsy towards precision medicine.
