Fanzors, a family of eukaryotic RNA-guided DNA endonucleases

Fanzor proteins represent the first confirmed family of RNA-guided DNA endonucleases in eukaryotes. Originally identified in 2013 as TnpB homologs, Fanzors remained functionally uncharacterized until 2023, when three independent research groups demonstrated their activity as programmable nucleases. Comprehensive bioinformatic analysis revealed over 3000 unique Fanzor sequences across diverse eukaryotic phyla and viruses. Fanzors share core mechanisms with their prokaryotic counterparts, utilizing a RuvC domain for DNA cleavage and requiring a Fanzor RNA (ωRNA) for targeting. However, they exhibit distinctive features, including diverse target adjacent motif preferences, extended ωRNA structure, and RuvC domain rearrangements. The eukaryotic origins of Fanzors make them promising tools for mammalian genome editing, with initial studies demonstrating successful editing in human cells without extensive engineering.