In bacteria, an alternative CRISPR/Cas system, called CASTs, can modify large stretches of DNA at once. American researchers discovered a large number of new CAST variants. This increases the chance that we will find a variant that also works in mammals.
Few scientific techniques can achieve as much as DNA-editing technique CRISPR/Cas. The classic CRISPR/Cas systems, which originally come from bacteria, make changes in genes with small cuts. Over the years, researchers have also discovered another system in bacteria that can modify entire parts of the genome at once: CASTs. That stands for CRISPR associated transposons, pieces of DNA that place themselves in different places in the genome using CRISPR.
With an extensive database search, American researchers have now found a whole number of new CASTs variants in bacteria. Should one of these variants also work in mammals, scientists have a hugely influential technique at their disposal.
Pair of scissors
The operation of classic CRISPR/Cas systems can be compared to scissors: small, targeted cuts make it possible to safely and precisely introduce new pieces of DNA into the genome. ‘This makes the technique particularly strong at cutting genes, but repairing genetic errors is difficult and not very efficient,’ explains geneticist Maarten Geurts from Utrecht University and the Hubrecht Institute. He is not involved in this investigation.
‘With CASTs we could potentially insert many genes into the genome at the same time, each of which has a different function,’ says molecular biologist Ilya Finkelstein from the University of Texas at Austin in a press release. This makes it possible, for example, to treat complex diseases whose cause cannot be traced back to a single gene.
gold diggers
Almost all types of bacteria have CRISPR systems. Although scientists have already researched many, they continue to look for CAST variants that are of interest for use in mammals. Using a supercomputer, the American research team therefore searched the world’s largest database of microbial pieces of genome. ‘The term for this is bio-prospectingFinkelstein says. “It was like rummaging through a lot of silt and junk to find the occasional gold nugget.”
They certainly found those gold nuggets: they found 1476 new alleged CASTs. The team has already characterized some variants and certainly plans to explore more. Finkelstein predicts that most will actually be CASTs.
Future
It remains to be seen whether all these new CAST variants really work well and safely in mammals. Arithmetic Biologist Claus Wilke, also from the University of Texas at Austin, is hopeful: “If you only have a few CASTs, it’s unlikely you’ve got your hands on the best. But if you have more than a thousand, that’s a different story. It’s a good starting point to find out which CAST variants are the easiest to work with, or which are the most efficient or accurate.’
‘Everything stands or falls with the applicability in the lab’, responds Geurts. ‘This finding certainly helps in the search for effective CASTs, but there are now also other techniques that have a comparable function. These already work in mammals in the lab.’ He emphasizes that the find is nevertheless interesting: ‘For the application, it is mainly about ease of use and how well the CASTs work in cells, animal models and ultimately in humans. The future will show this’.