Scientists at MIT’s McGovern Institute for Brain Research recently made a groundbreaking discovery. They identified thousands of diverse species, ranging from snails to algae to amoebas, that possess programmable DNA-cutting enzymes known as Fanzors. These enzymes, guided by RNA, can be tailored to cut DNA at specific locations, much like the widely used CRISPR gene-editing system.
RNA-guided biology, which enables the creation of programmable tools, has proven invaluable in research and medicine. The newfound diversity of Fanzor enzymes offers a vast resource for developing new tools.
CRISPR, originally a bacterial defense system, has revolutionized DNA modification in the laboratory. The RNA-guided enzymes adapted from CRISPR have accelerated research and facilitated experimental gene therapies.
Beyond CRISPR, scientists have discovered various RNA-guided enzymes in the bacterial world, each with unique features beneficial in lab settings. Fanzors represent a novel frontier in RNA-guided biology because they are the first such enzymes found in eukaryotic organisms, which include plants, animals, and fungi.
One exciting prospect is that enzymes naturally evolved in eukaryotes may be better suited to function safely and effectively within the cells of other eukaryotic organisms, including humans. Some Fanzors have already shown efficiency in cutting specific DNA sequences in human cells.
Prior to this study, hundreds of Fanzors were known among eukaryotic organisms. However, the MIT team significantly expanded this knowledge by discovering over 3,600 Fanzors, categorizing them into five enzyme families, and revealing their long evolutionary history.
Fanzors likely evolved from bacterial enzymes known as TnpBs, which cut DNA guided by RNA. The research indicates that these bacterial predecessors entered eukaryotic cells more than once, potentially transmitted by viruses or symbiotic bacteria. Once inside eukaryotes, Fanzors developed features suited to their new environment, such as signals for entering cell nuclei to access DNA.
Through genetic and biochemical experiments, the researchers found that Fanzors possess a unique DNA-cutting active site, enabling precise target cutting without the promiscuous activity observed in TnpBs. In tests with human cells, certain Fanzors efficiently cut target DNA sequences.
With further research, the scientists hope to develop a range of sophisticated genome editing tools using Fanzors, opening up new possibilities in the world of RNA-guided systems within eukaryotic organisms.