Potential CRISPR alternative gene-editing tool occurs naturally in animals

CRISPR-Cas9 has been the household name of genetic engineering tools over the past decade, but there might be other, better ways. MIT scientists have now demonstrated an alternative called Fanzor, which is naturally found in animals so could be a better fit for human use.

The CRISPR gene-editing system was originally isolated from bacteria, which use an enzyme called Cas9 to snip out a section of a virus’s DNA and store it for later, to help them fight off that infection in the future. In 2012, scientists made the Nobel Prize-winning discovery that this process could be hijacked to edit DNA in living cells, which has since been used to treat diseases, grow better crops, and tweak bacteria to do some important things.

As successful as CRISPR has been so far, scientists have wondered if there are other similar systems at play in some of our closer relatives – after all, bacteria are about as far from us on the tree of life as it’s possible to get. And now, researchers at MIT have found a group of proteins that function much the same way, but in animals.

The breakthrough began with the team’s previous work, when a new class of DNA-cutting enzymes called OMEGAs was identified in bacteria. In that study, the researchers noted similarities between OMEGAs and a group of proteins called Fanzor. Importantly, Fanzor proteins occur in eukaryotes, the domain of life that includes animals and as such, humans.

In the new study, the team isolated Fanzors from fungi, algae, amoeba and clams, and investigated their biochemical roles. And sure enough, the proteins were found to cut DNA using nearby segments of RNA known as ωRNAs (omega-RNAs). This marks the first time this kind of mechanism has been discovered in eukaryotes.

The researchers found that Fanzor proteins are encoded inside “jumping genes” – those that can move around more freely than others. This suggests that they were originally transferred over from bacteria in the very distant past.

In the next tests, the scientists investigated how well Fanzors could function as gene-editing tools in human cells. It was able to both insert and delete genes at programmable places in the genome, with about 18% efficiency. That’s admittedly much lower than CRISPR, but the latter has built up a decade’s worth of improvements. On the other hand, Fanzor outperformed CRISPR in selectiveness, cutting its target DNA without damaging nearby segments.

All up, the team says Fanzor proteins could become a key tool in the gene editing toolbox, and its discovery suggests more are hiding out there still to be found.

The research was published in the journal Nature.

Source: MIT

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