Tuesday, 23 May 2017

A disposable genomic scalpel

Nature Communications reports on revolutionary biomedical approach patented by UniTrento

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Genetic treatments, which have been developed since the end of the ‘80s through genetic engineering, were seen as the ultimate solution to treat many conditions that are still incurable - like hereditary diseases (cystic fibrosis, muscular atrophy, haemophilia, type 1 diabetes), diseases caused by environmental factors (cancer, cardiovascular diseases, neurodegenerative diseases), and trauma, infections, strokes.

With gene therapies we can deliver into a patient’s cells a gene to treat his or her disease.

This represents a big step forward for medicine because, thanks to very efficient vectors (viruses that are rendered harmless), we can edit even those cells that are difficult to reach.

However, the enthusiasm of the scientific community for the potential of gene therapies has cooled down recently when scientists discovered their undesirable and uncontrollable side effects.

Now researchers all over the world want to identify safer and more efficient delivery methods for gene therapies, to “cut and paste the genome” leaving no trace and no genomic damage.

The challenge starts from CRISPR/Cas9, a molecule that is able to work as a “genomic scalpel”, removing from the patients’ DNA the gene that is responsible for a given disease. The problem is that if the molecule remains active in the patient’s system it can create unpredictable unwanted alterations. The molecule must be neutralized at the end of the procedure. But how can we do it?

The Centre for Integrative Biology (Cibio) of the University of Trento devised a solution, and the results of its research study were published yesterday in Nature Communications

«We have added to the viral vector that we use to deliver the molecule two extra RNA molecules» explained Anna Cereseto, biologist at Cibio, principal author of the paper. «One will target the specific site in the DNA where the “healing” CRISPR/Cas9 protein must be released. The other is targeted at itself. So when the protein edits the DNA, it also neutralizes itself. It is like a mirror effect. As a result, the “healing” protein remains in the system only as long as it is necessary to perform its function, and then it dissolves. In this way, we have put in place a self-limiting circuit that works efficiently without causing any complications».
«In Trento – added Cereseto – we are experimenting with this new approach to treat cystic fibrosis and spinal muscular atrophy (SMA), but its applications may extend to many other conditions, including, in particular, tumors».

The paper published in Nature Communications is the result of excellent teamwork within Cibio. The study was conducted by the research team led by Anna Cereseto, which includes Gianluca Petris and Antonio Casini, with the participation of biologists Francesca Demichelis and Luciano Conti.

The approach identified by Cibio laboratories has been patented (as SLiCES) by the University, and has tremendous potential applications. It might open new perspectives in the use of gene therapies to treat many other diseases.

However, the possible applications go beyond that because, as we have seen in recent years, progress in genome editing has positive effects in a variety of sectors: in medicine, with genetic surgery and drug development, in biology, with the study of genetic variants, and in “green” biotechnologies, with the development of new biomaterials, improvements in food production, and the production of fuels.