A specific DNA cutting system is widespread in all eukaryotic organisms. I study

Following the discovery of CRISPR-Cas in prokaryotes (bacteria and other single-celled organisms that lack a nucleus), scientists have long wondered whether similar systems exist in eukaryotes. The new study demonstrates that RNA-guided DNA cutting mechanisms are present in all kingdoms of life. The answer has now arrived, and it is affirmative. A group of researchers led by Feng Zhang of MIT and the Broad Institute of MIT and Harvard has in fact discovered the first RNA-guided programmable gene editing system in eukaryotes, organisms that include fungi, plants, animals and therefore ourselves. CRISPR, which earned its discoverers the Nobel Prize, is the progenitor of these systems, and is part of the defenses of bacteria against invasion by viruses; the system discovered in eukaryotes is instead based on a protein called Fanzor. Just like in the case of CRISPR, Fanzor uses an RNA guide to precisely target a target sequence of DNA to edit; and again as in the case of CRISPR, by changing the RNA sequence, Fanzor can be reprogrammed to cut any desired DNA target, however using a system already optimized to work in eukaryotic cells – including human ones.

Compared to CRISPR-based systems, those built starting from Fanzor are potentially more easily transferable to targets in cells and tissues of therapeutic interest, and further improvements compared to the system characterized so far will make it a valuable new technology for therapeutic genome editing human. Two years ago, members of the Zhang lab discovered that in addition to CRISPR/Cas, there is an additional class of RNA-guided gene editing systems in prokaryotes called OMEGAs in prokaryotes. These have the particularity of being connected to mobile elements of DNA, called transposons, which are able to “jump” from one point of the genome to another, and are part of that so-called “selfish DNA” which is the result of ancient viral integrations which, moving within a host genome, it generates variety in many different organisms (for example, in corn, where they were first discovered by Barbara McClintock). Perhaps it was precisely from these ancient molecular means used by transposons that systems recruited by the bacterial cell to attack the genome of invading viruses, such as CRISPR/Cas, were derived. However, the most interesting point in this case is that eukaryotes have also been found to contain molecular systems similar to OMEGA, which help transposons move through the genome: these are, in fact, proteins of the Fanzor type, which researchers have isolated in species of fungi, algae, amoebae and in a mollusc. Fanzor proteins molecular scissors )i.e. enzymes of the class of endonucleases) that cut DNA using RNAs known as ωRNA to target particular sites in the genome.

Unlike CRISPR proteins and similarly to OMEGAs, Fanzor enzymes are encoded in the eukaryotic genome within transposable elements, and the team’s phylogenetic analysis suggests that Fanzor genes migrated from bacteria to eukaryotes via so-called horizontal gene transfer . Fanzor and OMEGA are more ancestral than CRISPR, and are therefore among the most abundant proteins on the planet; they have probably passed by horizontal transfer back and forth between the genomes of very many species of even different kingdoms. To explore Fanzor’s potential as a genome editing tool, the researchers demonstrated that it can generate insertions and deletions at targeted genome sites within human cells. The researchers discovered that the Fanzor system was initially less efficient at cutting DNA than the CRISPR-Cas systems engineered in recent years, but thanks to some molecular biology techniques, they introduced a combination of mutations that increased its cutting activity. Fanzor by 10 times. Also, unlike some CRISPR and OMEGA systems, the research team found that a mushroom-derived Fanzor protein showed no “side effects,” i.e. shear defects in which more than the target + degraded nearby DNA.

At this point it is worthwhile to make further considerations, with respect to those of an applied nature which have rightly enthused both the authors and the community of researchers in the field of genetic editing. The fact that in all eukaryotes, and not just in bacteria, a natural system of specific DNA cutting is widespreadwhich also served at least originally to insert pieces of DNA (the transposons) in a specific way in the genome, or in correspondence with the target recognized by Fanzor, means that, if we want to use the words of James Shapiro, in plants, fungi and in animals there is a ready-made system for a sort of “natural genetic engineering”, capable both of changing the expression of the genome, through the mobilization of transposons to and from specific sites, and also, in the right conditions, of taking pieces of the genome of an organism and transferring it to completely different organisms, without the need for the infection of specific types of viruses.

Biological evolution, in terms of generation of the variety on which selection then acts, appears increasingly dominated by processes capable of extensively reshuffling the cards in play, without waiting for the long and improbable path of generation of sufficient varieties through random point mutations. In other words, natural genetic engineering is the norm, not the exception; and it is a casual and brutal process, much more than the one invented in human laboratories, which use the means discovered in nature, but direct their potential to precise ends and under controlled conditions. The fear of the mixing of genomes between different species, the verbal masquerade of the denomination TEA and other similar verbal, legal and philosophical acrobatics make one smile, in the face of the great promiscuity of nature, which shuns precisely that balance and stasis so sought after by ‘man.

Nature makes a mess in all possible ways, and from that genetic mess it draws the novelty that can survive better and exterminates the rest; fairy tales about long times, harmonic mechanisms and anything else invented out of fear of innovation are beautiful, but they don’t hold up in the face of the supreme innovator, or rather the great Darwinian flow of the living world. Let’s make good use of our knowledge and worry about that, instead of inventing myths about “natural” and not.