Good news! Amazing stuff!
"A team of researchers ... has uncovered the first programmable RNA-guided system in eukaryotes — organisms that include fungi, plants, and animals.
In a study in Nature, the team describes how the system is based on a protein called Fanzor. They showed that Fanzor proteins use RNA as a guide to target DNA precisely, and that Fanzors can be reprogrammed to edit the genome of human cells. The compact Fanzor systems have the potential to be more easily delivered to cells and tissues as therapeutics than CRISPR/Cas systems, and further refinements to improve their targeting efficiency could make them a valuable new technology for human genome editing. ...
led the biochemical characterization of the Fanzor proteins, showing that they are DNA-cutting endonuclease enzymes that use nearby non-coding RNAs known as ωRNAs to target particular sites in the genome. It is the first time this mechanism has been found in eukaryotes, such as animals. ..."
From the abstract:
"RNA-guided systems, which employ complementarity between a guide RNA and target nucleic acid sequences for recognition of genetic elements, play a central role in biological processes in both prokaryotes and eukaryotes. ... Although a few eukaryotic RNA-guided systems have been studied so far, such as RNA interference and ribosomal RNA modification, it remains unclear whether eukaryotes have RNA-guided endonucleases. Recently, a new class of prokaryotic RNA-guided system (termed OMEGA) was reported. The OMEGA effector TnpB is the putative ancestor of Cas12 and has RNA-guided endonuclease activity. TnpB may also be the ancestor of the eukaryotic transposon-encoded Fanzor (Fz) proteins, raising the possibility that eukaryotes are also equipped with CRISPR-Cas/OMEGA-like programmable RNA-guided endonucleases. Here we report the biochemical characterization of Fz, showing that it is an RNA-guided DNA endonuclease. We also show that Fz can be reprogrammed for human genome engineering applications. Finally, we resolved the structure of Spizellomyces punctatus Fz (SpuFz) at 2.7Å using cryogenic-electron microscopy, revealing the conservation of the core regions among Fz, TnpB and Cas12, despite diverse cognate RNA structures. Our results show that Fz is a eukaryotic OMEGA system, demonstrating that RNA-guided endonucleases are present in all three domains of life."
Fanzor is a eukaryotic programmable RNA-guided endonuclease (no public access)
Cryo-EM map of a Fanzor protein in complex with ωRNA and its target DNA.
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