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Published on October 15, 2023
MIT Scientists Discover Thousands of Programmable DNA-Cutting Fanzor Enzymes in Algae, Snails, and AmoebasSource: SmallRex, CC BY-SA 4.0, via Wikimedia Commons

MIT's McGovern Institute for Brain Research scientists have unearthed thousands of programmable DNA-cutting Fanzor enzymes in several organisms such as snails, algae, and amoebas. As highlighted in MIT News, these RNA-guided enzymes can be programmed to cut DNA at designated areas, resembling the bacterial enzymes of the renowned CRISPR gene-editing system. The discovery potentially aids in producing innovative tools for medicine and research.

The discovery of Fanzor enzymes' natural diversity presents a wealth of prospects for scientists. Before this finding, hundreds of Fanzors were identified in eukaryotic organisms (organisms encompassing membrane-bound nuclei). However, Omar Abudayyeh and Jonathan Gootenberg, both McGovern Fellows, led recent in-depth investigations and expanded our comprehension of these enzymes by a significant degree. They succeeded to spot more than 3,600 Fanzors in eukaryotes and the viruses that infect them, revealing a lengthy evolutionary history.

As widespread belief, Fanzors likely evolved from RNA-guided DNA-cutting bacterial enzymes—like TnpBs. They probably entered eukaryotic cells, leading to their evolution, repeatedly via transmissions from symbiotic bacteria or viruses. Fanzors are considered the premier RNA-guided enzymes discovered in eukaryotic organisms. Therefore, scientists think that they might be the optimal candidates to function with optimum efficiency and safety in eukaryotic organisms' cells, which include human cells.

This research, inevitably, is set to advance our understanding of RNA-guided biology, with the potential to introduce substantial progress in experimental gene therapies and gene editing. The MIT professor and McGovern investigator Feng Zhang, alongside Abudayyeh and Gootenberg, have previously conducted groundbreaking research, revolutionizing the methodologies for DNA modification. Their efforts have exponentially sped up research and rendered this process more productive.

According to the MIT News piece, scientists have found a multitude of distinct RNA-guide enzymes across the bacterial world, with many harboring invaluable traits for lab use. The onset of Fanzor exploration in eukaryotic organisms marks a new era in RNA-guided biology.

Zhang's team has showcased how Fanzor enzymes can be tweaked to accurately cut specific DNA sequences in human cells. Further, Abudayyeh and Gootenberg ascertained that a few Fanzors can target DNA sequences in human cells without the need for any optimization. Gootenberg has dubbed this achievement as "fantastic."

The focal point as per Abudayyeh: "Opening up the whole eukaryotic world to these types of RNA-guided systems is going to give us a lot to work on." The effectiveness of Fanzors' RNA-guided DNA-cutting activity in the development of advanced genome editing tools and unlocking gene therapy applications will be a significant focus.

Boston-Science, Tech & Medicine