Molecular Diagnosis and CRISPR Technology: HOLMES System
Overview:
Molecular diagnostics is the fastest-growing segment in the in vitro diagnostics (IVD) field, with technologies like PCR (polymerase chain reaction) and NGS (next-generation sequencing) being well-established and widely used. However, the complexity, cost, and need for sophisticated instruments limit their applicability in point-of-care, home testing, and rapid infectious disease detection. To address these limitations, Dr. Jin Wang's team has developed a novel molecular diagnostic system using the recently discovered CRISPR-Cas12 enzyme, named HOLMES (Highly Optic and Luminogenic Mismatch Erase System).
Key Discoveries and Development:
CRISPR-Cas12 Enzyme:
The team was the first internationally to discover that the CRISPR-Cas12 enzyme exhibits high-efficiency trans-cleavage of single-stranded DNA probes when activated by target nucleic acids.
Based on this discovery, they innovatively developed HOLMES for DNA/RNA molecular diagnostics.
Advantages of HOLMES:
High Sensitivity:Capable of detecting fewer than 10 molecules.
High Specificity:Can distinguish between common bacteria and superbugs.
Speed:Provides results in about an hour, significantly faster than conventional molecular diagnostics like qPCR and NGS.
Cost-Effective:The reagents are inexpensive.
Simplicity:Designed to be user-friendly for various settings, from hospitals to customs and disease control centers.
HOLMESv2:
In 2018, the team identified a class of heat-resistant Cas12 proteins and developed HOLMESv2, an upgraded version of the original system.
HOLMESv2 enhances the versatility and robustness of the diagnostic platform, making it suitable for a wide range of detection scenarios, including agricultural quarantine and blood stations.
Research Directions:
The team is focused on several key areas within CRISPR-based diagnostics and gene editing:
Development of HOLMES/HOLMESv2:
Enhancing the nucleic acid rapid detection system to improve sensitivity, specificity, and ease of use.
CRISPR-based DNA In Vitro Editing and Standards:
Establishing reliable methods and standards for DNA editing using CRISPR technology.
CRISPR-based Gene Editing and Regulation:
Exploring new techniques for precise gene editing and regulation to expand the applications in various fields.
CRISPR-based Cancer Diagnostics:
Advancing innovative diagnostic tools for cancer detection and exploring tumor markers to facilitate early diagnosis and personalized treatment.
Publications and Collaborations:
The team has published extensively in high-impact journals such as Cell Research, Cell Discovery, Nucleic Acids Research, Hepatology, EBioMedicine, ACS Synthetic Biology, and Trends in Biotechnology. Their work has garnered significant attention and adoption by other research teams and IVD companies worldwide.
By addressing the complexities and limitations of existing molecular diagnostic technologies, the HOLMES system represents a significant leap forward in the field, offering high sensitivity, specificity, speed, and cost-effectiveness. This platform holds immense potential for applications in disease detection, screening, and personalized medicine, making it a valuable tool in modern healthcare.
