Thousands of Fanzor DNA cutters that may outperform CRISPR identified
Following on from the discovery of programmable DNA-cutting enzymes known as Fanzors, scientists have found that a diverse range of species possess these genetic 'scissors', which presents a massive opportunity in the development of new medicines, genetic therapies and biotechnology.
Scientists from the McGovern Institute for Brain Research at the Massachusetts Institute of Technology (MIT) have now identified more than 3,600 Fanzors. These RNA-guided enzymes are able to be programmed to cut DNA at targeted sites, editing genes like the bacterial Cas9 enzyme in CRISPR.
Just why this is a big deal is in the microbiology. Fanzors – which the researchers have now found in a diverse set of species, from fungi to mollusks – stem from eukaryote organisms. Cas9, is found in the simpler prokaryotic cell.
So while those simpler cells, such as those that bacteria possess, are very removed from humans on the evolutionary tree, CRISPR – clustered regularly interspaced short palindromic repeats – has nonetheless been hugely effective in ‘correcting’ genetic diseases and developing diagnostic systems, and is considered one of the greatest discoveries in modern medicine.
Harnessing Fanzors in a similar way has the potential to be even more impactful, simply because these genetic scissors are better aligned with our cellular makeup.
“People have been searching for interesting tools in prokaryotic systems for a long time, and I think that that has been incredibly fruitful,” said McGovern Fellow Jonathan Gootenberg. “Eukaryotic systems are really just a whole new kind of playground to work in.”
CRISPR is a well-known bacterial defense mechanism to protect against foreign elements, helping to preserve the genetic code of the organism. Fanzors most likely evolved in eukaryotic cells through viral transmission or symbiotic bacteria, and specifically bacterial enzymes TnpBs, and were conserved due to their usefulness.
And due to the more complex nature of eukaryotic cell structure, the enzymes evolved distinct features such as being able to enter cell nuclei to access DNA.
Because of this, Fanzors appear to be more precise with their DNA-cutting target sites, compared to TnpB. And as such, hold immense promise for the future of gene therapies.
“RNA-guided biology is what lets you make programmable tools that are really easy to use,” said McGovern Fellow Omar Abudayyeh. “So the more we can find, the better.
“Opening up the whole eukaryotic world to these types of RNA-guided systems is going to give us a lot to work on,” he added.
The research was published in Science Advances.