CRISPR-based rapid molecular diagnostic tests for fusion-driven leukemias.

Area of Science:

• Molecular diagnostics
• Oncology
• Biotechnology

Background:

• Fusion oncogenes are critical for cancer diagnosis and treatment selection.
• Current molecular diagnostics for fusion-driven leukemias are not widely accessible, hindering timely treatment, especially in community hospitals and low-resource areas.

Purpose of the Study:

• To develop and validate CRISPR-based RNA-fusion transcript detection assays for diagnosing fusion-driven leukemias.
• To enable rapid, accessible molecular diagnostics outside of specialized laboratories.

Main Methods:

• Development of CRISPR-based RNA-fusion transcript detection assays utilizing SHERLOCK (specific high-sensitivity enzymatic reporter unlocking).
• Validation of assays using patient samples from APL and CML cases and dried blood spots from low-resource settings.

Main Results:

• The developed SHERLOCK assays demonstrated 100% sensitivity and specificity in diagnosing APL and CML.
• Assay optimizations were identified to facilitate use in non-tertiary cancer centers and clinical laboratories.

Conclusions:

• CRISPR-based SHERLOCK assays offer a sensitive and specific method for diagnosing fusion-driven leukemias.
• These rapid, point-of-care diagnostics can significantly improve patient outcomes by expanding access to timely diagnosis and targeted therapies.