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Spanish scientists revive 2,600-million-year-old proteins to fight current diseases

An international research team has for the first time reconstructed the ancestors of the known system CRISPR Cas 2600 million years ago and studied its evolution over time. The results were published in the journal Nature MicrobiologyIt suggests that the regenerated systems not only work, but are more versatile than current versions and could have “breakthrough applications” in gene editing and disease treatment, the authors note.

In a project led by CIC nanoGUNE researcher Ikerbask Raul Perez-JimenezTeams from CSIC, University of Alicante, Center for Biomedical Research on Rare Diseases (CIBERER) and other state and international institutions are participating,

The acronym CRISPR is a Repetitive sequences in the DNA of bacteria and archaea (prokaryotic organisms). Between replications, these microorganisms retain fragments of genetic material from the viruses that infected their ancestors, allowing them to sense whether the infection will reoccur and defend themselves by cutting out the invaders’ DNA using Cas proteins associated with these replications.

The CRISPR Cas Molecular Scissors Let it be today Cut and paste pieces of genetic material in any cell, making it possible to use it for DNA editing.

Current research efforts are directed at detn New versions of CRISPR Cas systems with different properties in the most remote places of the planet. For this, the systems of various species that inhabit extreme environments are studied, or molecular design techniques are used to modify them. A radically different way of finding new systems is to look for them in the past, which is the basis of this research.

Reconstruction of proteins and genes of extinct organisms

NanoGUNE Nanobiotechnology group headed by Raul Perez-Jimenez, has spent years studying the evolution of proteins from the origin of life to the present day. They reconstruct the ancestors of proteins and genes from extinct organisms to see what properties they have and whether they have uses. Biotechnological applications.

It is time travel that is carried out through bioinformatics techniques. In the new paper, they were able to reconstruct the evolutionary history of CRISPR Cas systems for the first time, from their 2.6 billion-year-old ancestors to the present day.

The research team performed computational reconstruction of ancestral CRISPR sequences, synthesized them, and studied and confirmed their functionality.

“Surprisingly, we can revive Cas proteins that must have existed billions of years ago and find that they already had the ability to act as gene editing tools, which we have now confirmed by successfully editing genes in human cells.” explains. Louis MontoliuCSIC National Center for Biotechnology (CNB-CSIC) and CIBERER researcher and group leader who functionally confirmed this ancestral Cas in cultured human cells.

New applications with archaic systems

Another interesting finding of the study is that the CRISPR Cas system has become more complex over time, which is a sign that. adaptive character As it adapts to the new viral threats that bacteria have faced throughout evolution.

“This study represents an extraordinary advance in our understanding of the origin and evolution of CRISPR Cas systems. How the selective pressure of viruses over billions of years honed a rudimentary mechanism that wasn’t very selective in the beginning until it turned it into a sophisticated defense mechanism that can distinguish with great precision between the genetic material of unwanted invaders, which it must destroy, and its own DNA, which it must preserve. “, adds the researcher of the University of Alicante and the discoverer of the CRISPR Cas technique. Francis Mojica.

In terms of use, “the work represents an original way of approaching Development of CRISPR tools Generating new tools and improving existing tools of existing organizations,” Mojica adds.

“Current systems are very complex and have been adapted to function in bacteria. When the system is used outside this environment, for example in human cells, the immune system causes rejection and there are also certain molecular restrictions that limit its use. Interestingly, some of these limitations disappear in ancestral systems, making them more versatile for new applications,” Pérez-Jimenez emphasizes.

in turn Miguel Angel MorenoThe head of the genetics service at the Ramón y Cajal Hospital and CIBERER researcher points out that “the sense that the ancestral nuclease can have, because it does not recognize certain regions of the genome so specifically, makes it a more versatile tool. Correct mutations that were previously uneditable or were corrected in an inefficient manner”.

His group developed a tool that enabled the characterization Massive sequencing and bioinformatics analysisEffect of progenitor-derived genome editing on human cells in culture.

Ilenia JabaleraThe NanoGUNE project researcher claims that “this scientific breakthrough makes it possible to have genetic editing tools with properties different from the current ones, much more flexible, which opens up new ways to manipulate DNA and treat diseases such as e.g. ALS, cancer and diabetes, or even as a diagnostic tool. ”

Source: El Diario





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