A diverse set of species, from snails to algae to amoebas, make programmable DNA-cutting enzymes called Fanzors. Scientists at the MIT have identified thousands of them. This was initially announced early this year but has gone into publication now.
Fanzors are RNA-guided enzymes that can be programmed to cut DNA at specific sites, much like the bacterial enzymes that power the widely used gene-editing system known as CRISPR.
Fanzors gives scientists an extensive set of programmable enzymes that might be adapted into new tools for research or medicine. Fanzors likely evolved from RNA-guided DNA-cutting bacterial enzymes called TnpBs. In fact, it was Fanzors’ genetic similarities to these bacterial enzymes that first caught the attention of the scientists. More than 3600 fanzors have been identified.
Compared to CRISPR-Cas systems, which range from about 1,000 to 1,600 amino acids, Fanzor systems are more compact, ranging from 400 to 700 amino acids, and could potentially be more easily delivered to cells and tissue.
CRISPR, an ancient bacterial defense system, has made it clear how useful RNA-guided enzymes can be when they are adapted for use in the lab. CRISPR-based genome editing tools developed by MIT professor and McGovern investigator Feng Zhang, Abudayyeh, Gootenberg, and others have changed the way scientists modify DNA, accelerating research and enabling the development of many experimental gene therapies.
Fanzors were the first such enzymes to be found in eukaryotic organisms—a wide group of lifeforms, including plants, animals, and fungi, defined by the membrane-bound nucleus that holds each cell's genetic material. (Bacteria, which lack nuclei, belong to a group known as prokaryotes.)
"People have been searching for interesting tools in prokaryotic systems for a long time, and I think that that has been incredibly fruitful," says Gootenberg. "Eukaryotic systems are really just a whole new kind of playground to work in."
One hope, Abudayyeh and Gootenberg say, is that enzymes that naturally evolved in eukaryotic organisms might be better suited to function safely and efficiently in the cells of other eukaryotic organisms, including humans. Zhang's group has shown that Fanzor enzymes can be engineered to precisely cut specific DNA sequences in human cells. In the new work, Abudayyeh and Gootenberg discovered that some Fanzors can target DNA sequences in human cells even without optimization. "The fact that they work quite efficiently in mammalian cells was really fantastic to see," Gootenberg says.
Fanzors are RNA-guided enzymes that can be programmed to cut DNA at specific sites, much like the bacterial enzymes that power the widely used gene-editing system known as CRISPR.
Fanzors gives scientists an extensive set of programmable enzymes that might be adapted into new tools for research or medicine. Fanzors likely evolved from RNA-guided DNA-cutting bacterial enzymes called TnpBs. In fact, it was Fanzors’ genetic similarities to these bacterial enzymes that first caught the attention of the scientists. More than 3600 fanzors have been identified.
Compared to CRISPR-Cas systems, which range from about 1,000 to 1,600 amino acids, Fanzor systems are more compact, ranging from 400 to 700 amino acids, and could potentially be more easily delivered to cells and tissue.
CRISPR, an ancient bacterial defense system, has made it clear how useful RNA-guided enzymes can be when they are adapted for use in the lab. CRISPR-based genome editing tools developed by MIT professor and McGovern investigator Feng Zhang, Abudayyeh, Gootenberg, and others have changed the way scientists modify DNA, accelerating research and enabling the development of many experimental gene therapies.
Fanzors were the first such enzymes to be found in eukaryotic organisms—a wide group of lifeforms, including plants, animals, and fungi, defined by the membrane-bound nucleus that holds each cell's genetic material. (Bacteria, which lack nuclei, belong to a group known as prokaryotes.)
"People have been searching for interesting tools in prokaryotic systems for a long time, and I think that that has been incredibly fruitful," says Gootenberg. "Eukaryotic systems are really just a whole new kind of playground to work in."
One hope, Abudayyeh and Gootenberg say, is that enzymes that naturally evolved in eukaryotic organisms might be better suited to function safely and efficiently in the cells of other eukaryotic organisms, including humans. Zhang's group has shown that Fanzor enzymes can be engineered to precisely cut specific DNA sequences in human cells. In the new work, Abudayyeh and Gootenberg discovered that some Fanzors can target DNA sequences in human cells even without optimization. "The fact that they work quite efficiently in mammalian cells was really fantastic to see," Gootenberg says.
