Guide RNA (gRNA) (gRNA)

Guide RNA (gRNA) is a synthetic RNA molecule that serves as the programmable component of CRISPR-Cas genome editing systems. It consists of a scaffold sequence that binds to a Cas nuclease, such as Cas9 or Cas12, and a spacer sequence that is complementary to a specific genomic DNA or transcriptomic RNA target. By modifying the spacer sequence, researchers can program the CRISPR complex to target virtually any site in the genome, enabling precise gene knockout, insertion, or base editing. While gRNA is a therapeutic agent rather than a traditional drug target, it is the central element of RNA-guided therapies like Exagamglogene autotemcel (Casgevy), which is used to treat sickle cell disease and beta-thalassemia. The primary therapeutic challenges associated with gRNA include ensuring high specificity to avoid off-target effects at unintended genomic sites and managing the potential immunogenicity of the RNA-protein complex. Safety monitoring in clinical applications often involves deep sequencing to detect unintended mutations and monitoring for adverse immune responses.

Other names

sgRNASingle guide RNAcrRNAtracrRNACRISPR RNAProgrammable RNARNA guide

RNA-guided DNA cleavage followed by non-homologous end joining (NHEJ) or homology-directed repair (HDR)