New Eukaryotic Genome-Editing Protein Shows Potential for Future of Gene Editing
The new breakthrough and structural study of Fanzor2 by the St. Jude Children’s Research Hospital describes a versatile gene-editing tool that potentially can work even better and replace CRISPR-Cas9.
Scientists at St. Jude Children’s Research Hospital have discovered a new genome editing player called Fanzor2. Scientists have utilized high-resolution cryo-electron microscopy to explore structural mechanisms of the small eukaryotic protein and make the present gene-edited technology look radically new in the near future.
What is Fanzor2 ?
RNA-guided endonucleases, which were previously believed to exist only in prokaryotes, have now been found in eukaryotes and termed as Fanzors. The Fanzor family consists of two classes: Fanzor1 and Fanzor2. In this report, structural biologists from St. Jude introduced the cryo-electron microscopy structure of Fanzor2 from Acanthamoeba polyphaga mimivirus. The unique architecture of ωRNA, the active center of the protein, and the features of the motif recognition that involves transposon-adjacent motifs are highlighted by the structure. This research gives an idea about how RNA-guided endonucleases diversified as compared to structures for Fanzor1 and TnpB.
Fanzor2 is an RNA-guided nuclease, recently discovered in eukaryotes, belonging to a family of transposon-associated proteins. It has all the closest resemblance to TnpB, a protein from bacteria and is known as a precursor to those CRISPR-Cas that are currently used for genome editing applications. Fanzor2 is smaller in size and may be more efficient compared to CRISPR-Cas9 for that reason, along with its structure and mechanism, and it even stands to be an exception for new avenues in the field of genomic engineering in the future.
Cryo-EM reconstruction (top) and atomic model (bottom) of ApmFz2 ternary complex
How Fanzor2’s Small Size Boosts Gene Editing Efficiency
Fanzor2 is smaller than CRISPR-Cas9 and Cas12, offering great promise for a much more efficient system of genome editing. The compact structure increases functionality while it opens new pathways to optimize gene-editing techniques for therapeutic use.
What this cryo-EM study reveals from the researchers is how Fanzor2 interacts with its native RNA guide and DNA target. Such structural insight underscores a unique relationship between the RNA and protein constituents of Fanzor2, which separates it from others that belong to the same class of nucleases. It hints at a new level of malleability in how such proteins can be engineered for specific applications.
A New Path for Protein Engineering
Dr. Kellogg emphasized the structural diversity of RNA-guided nucleases, whose structural diversity will provide a clue to designing more efficient, customizable genome-editing tools tailored to specific therapeutic needs as more of Fanzor2’s capabilities unfold.
The very exciting new direction through which Fanzor2 genome-editing technology goes on is already off to a very promising start. Its compact size presents promising applications in applications requiring high precision within biomedicine, and being a two-module protein will surely hold much promise. Much is yet to be learned and discovered about optimizing Fanzor2, but its next-generation tool potential is evident.
More efficient and targeted gene editing may lie at the door of this discovery for those researchers and innovators of the field, maybe in transformative ways that we can hardly, at present imagine, for therapeutic applications.
Know more about Fanzor2 here.
