DNA-Editing Molecules Discovered Widespread in Organisms like Algae, Snails, and More
Fancy DNA-Choppers: A Look at Fanzor Enzymes
In the vibrant world of genetic engineering, a fresh breed of DNA-cutting enzymes called Fanzors has caught the eye of scientists. Thanks to a groundbreaking study led by researchers at MIT's McGovern Institute for Brain Research, the diversity of these enzymes has been demystified. Fanzors, much like their bacterial counterparts that power CRISPR, can be programmed to snip DNA at specific sites, opening a doorway to a treasure trove of tools for research and medicine.
"In genetics, variety is the spice of life," remarks McGovern Fellow Omar Abudayyeh, who spearheaded the research with his fellow McGovern Fellow Jonathan Gootenberg. "The more we find, the better!"
Long renowned for its versatility in the lab, CRISPR — a process borrowed from ancient bacterial defense mechanisms — has revolutionized gene editing. MIT professor and McGovern investigator Feng Zhang, alongside Abudayyeh, Gootenberg, and their colleagues, have drastically altered the way geneticists manipulate DNA, accelerating research and paving the way for numerous experimental gene therapies.
Beyond CRISPR, researchers have unmasked other RNA-guided enzymes scattered throughout the microbial world, each with distinct useful qualities. The recent discovery of Fanzors — reported by Zhang's group earlier this year — marks a new milestone in the realm of RNA-guided biology. Fanzors, the first such enzymes to be found in eukaryotic organisms, lead us into uncharted territory.
"There's a whole new playground out there just waiting to be explored," muses Gootenberg.
One promising prospect is that enzymes developed through evolution in eukaryotic organisms may function more safely and efficiently within the cells of other eukaryotes, including humans. The team found that Fanzor enzymes can be engineered to deftly cut specific DNA sequences in human cells. In fact, some Fanzors could slice target sequences in human cells without any optimization necessary. "It was truly amazing to witness how well they performed," shares Gootenberg.
With their extensive search led by lab member Justin Lim, Abudayyeh and Gootenberg expanded the known assortment of Fanzor enzymes by an order of magnitude, unearthing more than 3,600 of these toolboxes within eukaryotes and the viruses that infect them. By comparing the enzymes' makeup and identifying five different families, the researchers traced an evolutionary history stretching back to RNA-guided DNA-cutting bacterial enzymes called TnpBs, providing a fascinating connection between these distant relatives.
These bacterial predecessors likely entered the eukaryotic world more than once, with some transmission occurring through viruses and others through symbiotic bacteria. Post-transference, the enzymes evolved features tailored to their new environment, such as a signal allowing them to infiltrate the cell nucleus.
In genetic and biochemical experiments conducted by biological engineering graduate student Kaiyi Jiang, the team learned that Fanzors have evolved a separate DNA-cutting active site from their bacterial ancestors, allowing for more precise cuts when compared to targeting sequences in a test tube. When guided by RNA, certain Fanzors could cut target sequences in human cells with about a 10-20% efficiency.
With further research, Abudayyeh and Gootenberg envision a dazzling array of advanced genome editing tools developed from Fanzors. "This is a new frontier, and they have many capabilities," beams Gootenberg.
As researchers delve deeper into the magical world of Fanzors, the possibilities for genetic engineering grow ever brighter. "Exploring the entire eukaryotic realm for RNA-guided systems is going to provide us with a wealth of material to work with," adds Abudayyeh.
- Researchers, led by Omar Abudayyeh and Jonathan Gootenberg, at MIT's McGovern Institute for Brain Research have discovered a new breed of DNA-cutting enzymes called Fanzors, expanding the scope of research and medicine in genetic engineering.
- The team, including CRISPR pioneer Feng Zhang, found that Fanzor enzymes can be programmed to snip DNA at specific sites, opening a doorway to a variety of tools for research and medicine.
- Beyond CRISPR, the researchers have discovered Fanzors, the first RNA-guided enzymes to be found in eukaryotic organisms, lead us into uncharted territory in the realm of RNA-guided biology.
- Gootenberg muses that enzymes developed through evolution in eukaryotic organisms may function more safely and efficiently within the cells of other eukaryotes, including humans.
- In fact, some Fanzors could slice target sequences in human cells without any optimization necessary, according to Gootenberg.
- With further research, Abudayyeh and Gootenberg envision a dazzling array of advanced genome editing tools developed from Fanzors, potentially benefiting various medical-conditions and health-and-wellness.
- Abudayyeh adds that exploring the entire eukaryotic realm for RNA-guided systems is going to provide them with a wealth of material to work with, leading to future discoveries in environment-related science and mental health journal reports.
