Spanish scientists ‘resurrect’ proteins from 2,600 million years ago: “They could have revolutionary applications”

An international research group has reconstructed for the first time ancestors of the well-known CRISPR-Cas system from years ago. 2.6 billion years and has studied its evolution over time. The results suggest that the revitalized systems “not only work, but also are more versatile than current versions and could have revolutionary applications.”

The prestigious scientific journal Nature Microbiology has published the results of this research which, in the opinion of the research team, “opens New avenues for gene editing” Thus, new paths are opened in the manipulation of DNA and in the treatment of diseases such as cancer or diabetes.

In the project, led by CIC nanoGUNE researcher Ikerbasque Raul Perez-JimenezTeams from the Higher Council for Scientific Research, the University of Alicante, the Network Biomedical Research Center for Rare Diseases (CIBERER), the Ramón y Cajal Hospital-IRYCIS and other state and international institutions participate.

The acronym CRISPR is the name of repetitive sequences present in the DNA of bacteria and archaea (prokaryotic organisms). Between repetitions, these microorganisms harbor fragments of genetic material from viruses that have infected their ancestors, “which allow them to recognize if the infection is repeated and defend themselves by cutting the DNA of the invaders using Cas proteins associated with these repetitions,” they explained. from CIC nanoGUNE.

“Cut and paste” DNA

It is a mechanism (CRISPR-Cas system) of antiviral defense. CRISPR-Cas technology allows today to “cut and paste” pieces of genetic material into any cellwhich makes it possible to use it for edit dna.

Current research efforts are focused on finding new versions of CRISPR-Cas systems with distinct properties across the planet. For this, systems of different species that inhabit extreme environments are explored or molecular design techniques are applied to modify them.

The nanoGUNE Nanobiotechnology group has spent years studying the evolution of proteins from the origin of life to the present day. They carry out ancestral reconstructions of proteins and genes from extinct organisms to observe what qualities they have and if they are usable in biotechnological applications.

In this work that has just been published in the journal Nature Microbiology, they have reconstructed for the first time the evolutionary history of CRISPR-Cas systemsfrom ancestors of 2.6 billion years ago to the present.

The research team has carried out the computational reconstruction of the ancestral CRISPR sequences, synthesized them, and studied and confirmed their functionality. “It is surprising that we can revitalize Cas proteins that must have existed billions of years ago and verifying that they already had the capacity to operate as genetic editing tools, something that we have confirmed today by successfully editing genes in human cells” explains Lluís Montoliu, a researcher at the National Center for Biotechnology of the CSIC (CNB-CSIC) and the CIBERER, and head of the team that has functionally validated these ancestral Cass in human cells in culture.

Another conclusion of the study is that the CRISPR-Cas system has become more complex over time, which “is a sign of its adaptive nature, which has been adapting to new threats of viruses that bacteria have suffered throughout evolution”, they have pointed out from the research center.

“Current systems are very complex and are adapted to function inside a bacterium. When the system is used outside that environment, for example, in human cells, the immune system causes a rejection and there are also certain molecular restrictions that limit its use In ancestral systems some of these restrictions disappearwhich gives them a increased versatility for new applications”, emphasizes Pérez-Jiménez.

Ylenia Jabalera, project researcher at nanoGUNE, maintains that “this scientific achievement makes it possible to have genetic editing tools with properties different from the current ones, much more flexible, which opens up new pathways in DNA manipulation and treatment of diseases such as ALS, cancer, diabetesor even as a disease diagnostic tool”.