CasProtein

CasProtein is a family of CRISPR-associated effector proteins that mediate the adaptive immune response in bacteria and archaea. Members form ribonucleoprotein complexes with CRISPR RNA guides to recognize and cleave foreign genetic material. The most well-known member is Cas9, a programmable DNA endonuclease, with Cas12 and Cas13 providing alternative nucleic acid targeting and cleavage activities. Cas proteins are categorized into several types (I–VI) based on their architecture and interference mechanisms. In typical systems, the Cas protein works with a CRISPR RNA (crRNA) and, in some types, a trans-activating crRNA (tracrRNA) or a single-guide RNA (sgRNA) to specify target sequences adjacent to a protospacer adjacent motif (PAM).

CasProtein technologies have become foundational in biotechnology. They enable genome editing in cells and organisms, transcriptional regulation using dead variants (CRISPRi/CRISPRa), and diagnostic platforms that detect specific nucleic acids with high sensitivity and specificity (e.g., SHERLOCK, DETECTR). Delivery methods include plasmids, viral vectors, and purified ribonucleoprotein complexes. Challenges include off-target activity, PAM constraints, and delivery efficiency. Ongoing discovery of diverse Cas proteins from environmental and uncultured microbes expands the toolkit for editing, regulation, and rapid diagnostics, while ethical and biosafety considerations guide their responsible use.