Clustered regularly interspaced short palindromic repeats-associated protein 9 (Cas9)

The CRISPR-associated protein 9 (Cas9) is an RNA-guided DNA endonuclease derived from the bacterial Type II CRISPR adaptive immune system, most notably from Streptococcus pyogenes (PubMed: 22745249). It functions by forming a complex with a guide RNA (gRNA) that directs the enzyme to a complementary 20-nucleotide DNA sequence adjacent to a protospacer adjacent motif (PAM), where it induces a precise double-strand break (UniProt: Q99ZW2). This system has been repurposed as a powerful therapeutic tool for permanent genome editing, enabling the correction of genetic mutations or the disruption of disease-causing genes (NIH, 2023). In 2023, the first CRISPR-based therapy, Exagamglogene autotemcel, was approved for the treatment of sickle cell disease and beta-thalassemia by editing the BCL11A enhancer in hematopoietic stem cells (FDA, 2023). Despite its transformative potential, therapeutic application requires careful monitoring for off-target effects and potential immune reactions to the Cas9 protein (Nature Medicine: 25, 2019).

Other names

CRISPR-associated protein 9Cas9 nucleaseRNA-guided DNA endonuclease Cas9SpCas9Csn1

RNA-guided site-specific cleavage of double-stranded DNA to induce targeted genomic modifications.