CRISPR-Cas13 represents a fundamentally different approach to programmable biology by targeting RNA instead of DNA. Discovered and characterized by Feng Zhang's lab at the Broad Institute, Cas13 proteins bind and cleave single-stranded RNA guided by a complementary crRNA. This RNA-targeting capability enables transient gene knockdown without permanent genomic changes, offering a reversible alternative to DNA editing that may be preferable for certain therapeutic and research applications.

The diagnostic potential of Cas13 has been commercialized through the SHERLOCK (Specific High-sensitivity Enzymatic Reporter UnLOCKing) platform, which exploits the collateral RNA cleavage activity of activated Cas13 to detect specific RNA sequences with attomolar sensitivity. Sherlock Biosciences has developed this technology for clinical diagnostics, including tests for infectious diseases and genetic variants. During the COVID-19 pandemic, SHERLOCK-based SARS-CoV-2 tests demonstrated the rapid deployability of Cas13 diagnostics for emerging public health threats.

Therapeutic applications of Cas13 are also advancing. Researchers have used Cas13 for programmable RNA knockdown as an alternative to RNA interference, with potential advantages in specificity and programmability. RNA editing applications use catalytically inactive Cas13 fused to ADAR deaminase domains to make precise A-to-I edits in transcripts, correcting disease-causing mutations at the RNA level. This approach avoids permanent genome changes while still achieving therapeutic effects, an appealing safety profile for conditions where reversibility is valued.