Wednesday, November 8, 2023

Thousands of DNA- Cutting Enzymes Found in Eukaryotes


Many eukaryotic organisms contain DNA cutting enzymes called Fanzors and scientists at MIT’s McGovern Institute for Brain Research have identified that there are thousands of them.  Fanzors are RNA- guided enzymes that can be programmed to cut DNA at specific sites and its diversity gives scientists a large set of programmable enzymes that could be adapted into new tools for research or medicine. These enzymes are much like bacterial enzymes known as CRISPR, bacterial enzymes that power the widely used gene editing system. CRISPRS have made clear how useful RNA guided enzymes can be when used in the lab. The CRISPR-based genome editing tools were developed by MIT professors and McGovern investigators. These editing tools have changed the way scientists modify DNA, accelerating research and enabling the development of a lot of different types of gene therapies. Fanzor enzymes can be programmed to cut specific DNA sequences and it has been discovered that Fanzors can target DNA sequences in humans without optimization. Fanzors likely evolved from the RNA-guided DNA-cutting bacterial enzymes called TnpBs. The traced evolutionary connections suggest that the TnpBs probably entered the eukaryotic cells, some had likely been transmitted by viruses and some were likely introduced by symbiotic bacteria. A feature that they had developed through evolution was having a signal that allows them to enter a nucleus of a cell, where they would have access to DNA. The research team determined that Fanzors evolved a DNA-cutting active site that is distinct from their predecessors. The active site seems to allow the enzyme to cut its target sequence more precisely than the ancestors of TnpB. When the other enzymes are targeted to a DNA sequence in a test tube, they become activated and cut other sequences in the tube, which is something that the Fanzors do not do. When the researchers used an RNA guide to direct the enzymes to cut specific sites in the DNA of human cells, it was found that certain Fanzors were able to cut the target sequences with about 10% to 20% efficiency. 

These new findings are very important as they could help with discovering different, sophisticated genome editing techniques. Hopefully, with the discovery of the diversity of Fanzors, enzymes naturally evolved in eukaryotes could be better suited to function safely and efficiently in other eukaryotes, including humans. This article was exciting to read because it indicates the promises of further discoveries of different editing techniques for DNA.


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