JUN 30, 2023 3:39 PM PDT

A New, CRISPR-Like Gene-Editing System is Discovered in Animals

WRITTEN BY: Carmen Leitch

The CRISPR gene editing system originated in bacteria, and is part of a defense that bacterial cells use against viruses. In CRISPR gene editing, a guide RNA brings a genome-cutting enzyme (typically Cas9) to a specific place in the genome, where a cut is made. This system has been modified, adapted, and used in many ways that have been revolutionary, triggering advances in the research lab, and has even treated disease in a small number of people. Now scientists have discovered another gene editing system in eukaryotic cells, which make up plants, animals, and fungi. It is based on a protein known as Fanzor, which also uses RNA as a guide that takes it to a specific place in the genome to make a cut.

Reporting in Nature, researchers have shown that Fanzor proteins can be reprogrammed so they target the DNA in human cells. Fanzors are also smaller, and are likely easier to deliver to cells compared to the CRISPR/Cas9 method. Much like CRISPR, this new technique will probably be altered and improved in a variety of ways before it can be brought to the clinic, but it opens up many new gene editing possibilities.

This research has also shown that mechanisms that cut DNA are not only found in bacterial or prokaryotic cells; all the kingdoms of life carry some system like it. This is the first time a DNA-cutting system has been discovered in eukaryotes.

Several years ago, we began to wonder what was beyond CRISPR, and whether there were other RNA-programmable systems in nature, said senior study author Feng Zhang, a Howard Hughes Medical Institute investigator and core member of the Broad Institute of MIT and Harvard, among many other appointments.

The research team identified and isolated Fanzors from various species including fungi, algae, and amoeba. A characterization of the proteins revealed their endonuclease power - they can cut DNA. They also use RNA molecules that do not code for protein to target specific genomic sequences. Fanzor proteins sit within the eukaryotic genome, in regions known as transposable elements. They also may have migrated to eukaryotes from prokaryotes during horizontal gene transfer.

The investigators are showed that Fanzors can create insertions and deletions at specific places in the human genome, though they were initially far less efficient at cutting DNA compared to CRISPR methods. With a systematic testing of different mutations in the Fanzor proteins, the scientists boosted Fanzor's activity ten times. They also appear to have low levels of off-target activity and do not seem to affect nearby DNA or RNA molecules.

The researchers are hopeful that Fanzors can be reprogrammed to edit specific places in the genome, and may one day be used in research or clinical treatments. There may also be better genome editors waiting to be revealed.

"Nature is amazing. There's so much diversity," said Zhang. "There are probably more RNA-programmable systems out there, and we're continuing to explore and will hopefully discover more."

Sources: Broad Institute of MIT and Harvard, Nature

About the Author
Bachelor's (BA/BS/Other)
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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