CRISPR-Cas enzymes: The toolkit revolutionizing diagnostics

Verosloff, Matthew S; Shapiro, Sarah J; Hawkins, Elizabeth M; Alpay, Emel; Verma, Deepika; Stanfield, Emma G; Kreindler, Lior; Jain, Sonal; McKay, Bridget; Hubbell, Shae A; Hendriks, Carley G; Blizard, Benjamin A; Broughton, James P; Chen, Janice S

The programmable nature of sequence-specific targeting by CRISPR-Cas nucleases has revolutionized a wide range of genomic applications and is now emerging as a method for nucleic acid detection. We explore how the diversity of CRISPR systems and their fundamental mechanisms have given rise to a wave of new methods for target recognition and readout. These cross-disciplinary advances found at the intersection of CRISPR biology and engineering have led to the ability to rapidly generate solutions for emerging global challenges like the COVID-19 pandemic. We further discuss the advances and potential for CRISPR-based detection to have an impact across a continuum of diagnostic applications. GRAPHICAL ABSTRACT AND LAY SUMMARY: The inherent programmability of CRISPR-Cas nucleases has enabled new methods for molecular diagnostics. Powered by the intersection of CRISPR biology and engineering, CRISPR-based diagnostics offer timely, accurate and actionable solutions across the continuum of testing applications.