A CRISPR-like mechanism in eukaryotes has been unraveled for the first time.
Animals, plants, and fungi are all members of the eukaryotes. And CRISPR is a well-known technique for editing genomes in humans and plants.
The newly identified system is based on a protein known as Fanzor, which is prevalent in eukaryotes.
Feng Zhang leads the new development from the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT.
They describe it as the “first programmable RNA-guided system” in eukaryotes.
The known CRISPR technique
To further grasp this new work, it is necessary first to understand the origin of CRISPR/Cas. CRISPR is short for clustered, regularly interspaced short palindromic repeats.
CRISPR technology is derived from prokaryotes, which include bacteria and other single-cell creatures without nuclei. In prokaryotes organisms, CRISPR is a family of repeating DNA sequences found in their genomes.
But what is its function? The CRISPR system primarily offers prokaryotes protection against invaders and provides them immunity.
The use of CRISPR-Cas9 to modify genes was viewed as a revolutionary biological tool for curing life-threatening human disorders back in 2012. Since then, it has been widely employed in cancer research, viral infections, and even in other industries like agriculture.
“CRISPR-based systems are widely used and powerful because they can be easily reprogrammed to target different sites in the genome,” said Zhang, the senior author of this new study, in an official release.
And Zhang’s lab has long wondered if eukaryotes host similar mechanisms.
“A number of years ago, we started to ask, ‘What is there beyond CRISPR, and are there other RNA-programmable systems out there in nature?’” said Zhang.
The new Fanzor-based system
After several years of research, the lab uncovered similar mechanisms in eukaryotes.
For this investigation, Fanzors were isolated from fungus, algae, and amoeba species, as well as a hard clam known as the Northern Quahog,
The authors found that Fanzor proteins were able to target DNA accurately by using RNA as a guide. This implies that Fanzors can be reprogrammed to edit human cell genomes.
“Biochemical characterization of the Fanzor proteins, showing that they are DNA-cutting endonuclease enzymes that use nearby non-coding RNAs known as ωRNAs to target particular sites in the genome,” explained the release.
The authors highlight that the “RNA-guided DNA-cutting process” has been observed in all eukaryotes.
Now, they intend to use Fanzor proteins present in eukaryotes to develop CRISPR-like technology.
“This new system is another way to make precise changes in human cells, complementing the genome editing tools we already have,” added Zhang.
Furthermore, the team believes that Fanzor has the potential to edit DNA more specifically when compared to CRISPR/Cas systems. The researchers noticed that “compact Fanzor systems” are more readily administered to specific cells and tissues as therapies than CRISPR/Cas systems.
However, they note that additional system refinements are needed to improve cell targeting efficiency. Nonetheless, it can potentially be a valuable new tool for human genome editing one day.
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