TRENT. A collection of molecular tools to rewrite DNA with even more efficient and precise genetic editing: this is the latest discovery from the University of Trento.
To combine their skills with a view to making advance therapies dedicated to genetic diseases They were Anna Cesereto And Nicola Segata of the department of cellular, computational and integrative biology: she leads a laboratory that develops advanced technologies for gene editing and their application for the treatment of diseases, he leads a laboratory of metagenomics in which he studies the diversity and characteristics of the human microbiome and the its role in health.
The intuition, described in an article published in the journal Nature Communication, led to identify new Crispr-Cas9 molecules in an intestinal bacterium that could have clinical development in the treatment of genetic diseases including those of the eye, such as retinitis pigmentosa, through subretina injections.
The scenario is research on genomic therapies that sees scholars working in various parts of the world to find new possibilities for treating genetic diseases and gene editing (the Crispr-Cas9 system) is based on the use of the Cas9 protein, a sort of molecular scissors that can be programmed to make specific modifications, cuts or replacements, of harmful DNA sequences and therefore correct disease-causing mutations.
Discovered in 2012 in the United States, this biotechnological tool has already led to a first approved therapy, a drug for sickle cell anemiaand now an acceleration of genomic research comes from the study from the University of Trento.
“We have found an effective, high-precision and above all more compact molecular scissor than other Crispr-Cas9 systems available today. This new Crispr-Cas9 molecule, as demonstrated by our experiments in the retina, will be easier to deliver to the organs that need to be treated in therapies for genetic diseases” comments Anna Ceresetoprotagonist since 2018 of research on the genomic corrector with the development of evoCas9.
Expanding the range of Crispr-Cas tools is indeed a necessary step to accelerate the development of therapies for genetic diseases and the advancement, it is explained, “can happen by modifying enzymes that are present in nature, as was the case for evoCas9, but discovering enzymes that have already evolved to function offers great advantages”.
And it is precisely the collaboration with Nicola Segata’s computational metagenomics laboratory that has allowed Anna Cereseto’s molecular virology laboratory to highlight a vast natural reserve of Crispr-Cas9 systems from which to draw valuable new tools for editing the human genome.
“Through interrogating a database of genomes from the human microbiome that we built over several years, we discovered a large reservoir of Cas9 with interesting properties for genome editing” the two professors tell us, specifying: “In the bacteria that populate the intestine we have discovered a great variety of Crispr-Cas9. In particular in Collinsellaa bacterial genus frequently present in our intestine, we identified the CoCas9 nuclease, a very active group of enzymes with small molecular dimensions, about a thousand amino acids.”
The sequencing of the entire microbiome through metagenomics, followed by laboratory reconstruction of assembled genomes, he then identified a huge variety of species and the discovery of a collection of new Cas9 nucleases, including CoCas9, contributes to enriching the “toolbox” for genome editing.
“Although the development of curative therapies for genetic diseases remains hampered by the difficulty of administration – finally explain Anna Cesereto and Nicola Segata – CoCas9, thanks to its small size, shows potential for gene therapy applications and is therefore a candidate for optimization through engineering approaches, which deserve further investigation. We are already working on clinical development.”
