Structural principles of CRISPR-Cas enzymes used in nucleic acid detection

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-based technology has revolutionized the field of biomedicine with broad applications in genome editing, therapeutics and diagnostics. While a majority of applications involve the RNA-guided site-specific DNA or RNA cleavage by CRISPR enzymes, recent successes in nucleic acid detection rely on their collateral and non-specific cleavage activated by viral DNA or RNA. Ranging in enzyme composition, the mechanism for distinguishing self-from foreign-nucleic acids, the usage of second messengers, and enzymology, the CRISPR enzymes provide a diverse set of diagnosis tools in further innovations. Structural biology plays an important role in elucidating the mechanisms of these CRISPR enzymes. Here we summarize and compare structures of three types of CRISPR enzymes used in nucleic acid detection captured in their respective functional forms and illustrate the current understanding of their activation mechanism.

Automated summary

CRISPR-based technology has revolutionized biomedicine through its applications in genome editing, therapeutics, and diagnostics. Recent studies have shown that CRISPR enzymes can also be used for nucleic acid detection by collateral and non-specific cleavage of viral DNA or RNA. The diverse compositions, self-foreign nucleic acid recognition mechanisms, usage of second messengers, and enzymology of CRISPR enzymes provide a wide range of diagnostic tools for further innovations. Structural biology plays a crucial role in understanding the activation mechanisms of these CRISPR enzymes.