CRISPR-associated protein 13 (Cas13) (Cas13)

CRISPR-associated protein 13 (Cas13) is a Type VI CRISPR effector that functions as an RNA-guided ribonuclease (Abudayyeh et al., 2016, Science). Unlike the more common Cas9 which targets DNA, Cas13 is specialized for the programmable recognition and cleavage of single-stranded RNA (ssRNA) (Konermann et al., 2018, Cell). The protein contains two Higher Eukaryotes and Prokaryotes Nucleotide-binding (HEPN) domains that provide its catalytic activity (UniProt, 2024). Upon binding to a target RNA sequence complementary to its guide RNA, Cas13 undergoes a conformational change that activates its nuclease activity, leading to target degradation (cis-cleavage) and, in some contexts, non-specific cleavage of nearby bystander RNA (trans-cleavage) (Gootenberg et al., 2017, Science). Cas13 is being actively developed as a therapeutic agent for viral infections, such as SARS-CoV-2 and influenza, by directly degrading viral RNA genomes (Blanchard et al., 2021, Nature Communications). It also holds promise for treating genetic disorders through RNA knockdown or, when fused to deaminases, through precise RNA base editing (Cox et al., 2017, Science). Current drug development focuses on delivering Cas13 via mRNA-lipid nanoparticles or viral vectors to modulate disease-associated transcripts without altering the underlying genome.

Other names

C2c2RNA-guided ribonucleaseType VI CRISPR-associated proteinCas13aCas13bCas13d

RNA-guided endoribonuclease activity involving the HEPN domains to cleave target RNA (cis-cleavage) and potentially non-specific bystander RNA (trans-cleavage) upon activation.