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Cas9d is a compact, Type II-D CRISPR-associated protein 9 (Cas9) ortholog derived from *Deltaproteobacteria*. Comprising only 747 amino acids, it is recognized as the smallest known member of the Cas9 family, a feature that facilitates efficient delivery via a single adeno-associated virus (AAV) vector due to its small genetic footprint (expression cassette <3.4 kb). Functionally, Cas9d acts as an RNA-guided endonuclease that targets and cleaves double-stranded DNA at sites adjacent to an NGG protospacer-adjacent motif (PAM). It utilizes a unique RNA-coordinated structural module for DNA targeting and exhibits significantly higher fidelity than the widely used *Streptococcus pyogenes* Cas9 (SpyCas9) by demonstrating lower tolerance for base mismatches. While primarily a research tool and platform technology for genome editing and base editing, its compact size and high precision make it a promising candidate for *in vivo* therapeutic applications.
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