An international research group has for the first time reconstructed ancestors dating back 2.6 billion years of the well-known CRISPR-Cas system, and studied their evolution over time. The results suggest that the revitalized systems not only work, but are more versatile than current versions and could have revolutionary applications. Nature Microbiology has published the results of this research, which, in the opinion of the research team, “opens up new avenues for gene editing.”
The acronym CRISPR refers to the repeated sequences present in the DNA of bacteria and archaea (prokaryotic organisms). Among the repeats, these microorganisms harbor fragments of genetic material from viruses that infected their ancestors; that enables them to recognize a repeat infection and defend themselves by cutting the invaders’ DNA using Cas proteins associated with these repeats. It is a mechanism (CRISPR-Cas system) of antiviral defense. This ability to recognize DNA sequences is the basis of their usefulness, and they act as if they were molecular scissors. Nowadays CRISPR-Cas technology enables pieces of genetic material to be cut and pasted into any cell, so that it can be used to edit DNA.
Current research efforts focus on finding new versions of CRISPR-Cas systems with distinct properties in the farthest reaches of the globe. To do this, systems of different species living in extreme environments are explored, or molecular design techniques are applied to modify them. A radically different way of finding new systems is to look for them in the past, which is in fact the basis of this research.
The Nanobiotechnology group at nanoGUNE, led by Raúl Pérez-Jiménez, has spent years studying the evolution of proteins from the origin of life right up to the present day. Ancestral reconstructions of proteins and genes from extinct organisms are carried out to see what qualities they have and whether they can be used in biotechnological applications. It is a journey back in time conducted by means of biocomputing techniques. In this work, which has just been published in the journal Nature Microbiology, the evolutionary history of CRISPR-Cas systems, from ancestors dating back 2.6 billion years to the present day, has been reconstructed for the first time.
The research team carried out the computational reconstruction of the ancestral CRISPR sequences, synthesized them, and studied and confirmed their functionality. “What is surprising is that we can revitalize Cas proteins that must have existed billions of years ago and find that they already had the capacity then to operate as gene editing tools; we have now confirmed that by successfully editing genes in human cells,” explained Lluís Montoliu, researcher at the National Biotechnology Center of the CSIC (CNB-CSIC) and CIBERER, and head of the team that has functionally validated these ancestral Cas proteins in human cells in culture.
Another interesting finding in the study is that the CRISPR-Cas system has gradually become more complex over time, which is a sign of the adaptive nature of the system; it has been gradually adapting to new virus threats that have been hanging over bacteria throughout evolution.
“This research signifies an extraordinary advance in knowledge about the origin and evolution of CRISPR-Cas systems. About how the selective pressure of viruses has over billions of years been fine-tuning rudimentary, initially not very selective machinery; this had been taking place until a sophisticated defense mechanism was produced; it is a mechanism capable of distinguishing with great precision between its own DNA, which it must preserve, and the genetic material of unwanted invaders, which it must destroy,” said University of Alicante researcher Francis Mojica, who discovered the CRISPR-Cas technique. On the applied side, “the work represents an original approach to the development of CRISPR tools to generate new tools and improve those derived from existing ones in current organisms,” added Mojica.
“Current systems are highly complex and are adapted to function within a bacterium. When the system is used outside this environment, for example in human cells, it is rejected by the immune system and there are also certain molecular restrictions that limit its use. Oddly enough, in ancestral systems some of these restrictions disappear, which gives these systems greater versatility for new applications,” said Pérez-Jiménez.
Miguel Angel Moreno, head of the Genetics Service at HRYC-IRYCIS-CIBERER, said, “The ingenuity that an ancestral nuclease could have, insofar as it does not so specifically recognize some regions of the genome, turns them into more versatile tools for correcting mutations that until now could not be edited or were not corrected very efficiently.” His team has developed the Mosaic Finder tool, which, by means of massive sequencing and bioinformatics analysis, has enabled the effect of genome editing carried out by these ancestral Cas in human cells in culture to be characterized.
Ylenia Jabalera, researcher in the project at nanoGUNE, says, “This scientific achievement can make available gene editing tools with properties different from the current ones, and which are much more flexible; that opens up new avenues in DNA manipulation and treatment of diseases such as ALS, cancer and diabetes, or even in diagnostic tools for diseases.”
News
Silver nanoparticles show promise in fighting antibiotic-resistant bacteria
In a new study, scientists with the University of Florida have found that a combination of silver nanoparticles and antibiotics is effective against antibiotic-resistant bacteria. The researchers hope to turn this discovery into viable [...]
Combating severe cancer with a new drug delivery system
Peritoneal cancer is difficult to treat and has a poor survival prognosis. But a new and effective nanomedicine delivery system is offering some hope. The company is called NaDeNo and is well underway with [...]
New Research Shows How Ketamine Acts As “Switch” in the Brain
According to a new study by researchers at Penn Medicine, ketamine, which is well-known as an anesthetic and is becoming increasingly popular as an antidepressant, dramatically reorganizes activity in the brain, almost as if [...]
Supercharged T Cells: A New Way To Kill Pancreatic Cancer With Minimal Side Effects
A new immunotherapy releases cancer-killing cytokines only within the tumor. Researchers at the University of California San Francisco (UCSF) have developed a new T cell-based immunotherapy that selectively targets cancer cells, producing a powerful anti-cancer cytokine [...]
AI has designed bacteria-killing proteins from scratch – and they work
An AI was tasked with creating proteins with anti-microbial properties. Researchers then created a subset of the proteins and found some did the job. An AI has designed anti-microbial proteins that were then tested [...]
Using nanoparticles, researchers can identify and deliver synergistic combinations of cancer drugs
Treating cancer with combinations of drugs can be more effective than using a single drug. However, figuring out the optimal combination of drugs, and making sure that all of the drugs reach the right [...]
Humanity May Reach Singularity Within Just 7 Years, Trend Shows
By one unique metric, we could approach technological singularity by the end of this decade, if not sooner. A translation company developed a metric, Time to Edit (TTE), to calculate the time it takes for professional [...]
HYPER (Highly Interactive Particle Relics) – A New Model for Dark Matter
Phase transition in early universe changes strength of interaction between dark and normal matter. Dark matter remains one of the greatest mysteries of modern physics. It is clear that it must exist, because without [...]
New Nanoparticles Deliver Therapy Brain-Wide and Edit Alzheimer’s Gene
Summary: Researchers have developed a new family of nano-scale capsules capable of carrying CRISPR gene editing tools to different organs of the body before harmlessly dissolving. The capsules were able to enter the brains of [...]
Cancer’s Secret Weapon? Enzyme That Protects Against Viruses May Fuel Tumor Evolution
An enzyme that defends human cells against viruses can help drive cancer evolution towards greater malignancy by causing myriad mutations in cancer cells, according to a study led by investigators at Weill Cornell Medicine. The [...]
Scientists Uncover Japanese Fruit Juice That May Help Prevent Lung Cancer
Using a mouse model, Japanese researchers unleash the likely mechanism of action of Actinidia arguta (sarunashi) juice on lung cancer development. Lung cancer is a leading cause of death in Japan and across the [...]
In-place manufacturing method improves gas sensor capabilities, production time
When used as wearable medical devices, stretchy, flexible gas sensors can identify health conditions or issues by detecting oxygen or carbon dioxide levels in the breath or sweat. They also are useful for monitoring [...]
In the core of the cell: New insights into the utilization of nanotechnology-based drugs
Novel drugs, such as vaccines against covid-19, among others, are based on drug transport using nanoparticles. Whether this drug transport is negatively influenced by an accumulation of blood proteins on the nanoparticle’s surface was [...]
The costly lesson from COVID: why elimination should be the default global strategy for future pandemics
Imagine it is 2030. Doctors in a regional hospital in country X note an expanding cluster of individuals with severe respiratory disease. Rapid whole-genome sequencing identifies the disease-causing agent as a novel coronavirus. Epidemiological [...]
How Artificial Intelligence Found the Words To Kill Cancer Cells
A predictive model has been developed that enables researchers to encode instructions for cells to execute. Scientists at the University of California, San Francisco (UCSF) and IBM Research have created a virtual library of thousands of “command sentences” [...]
Next-generation, light-activated nanotech for antibiotic-resistant superbugs
It's "lights out" for antibiotic-resistant superbugs as next-generation light-activated nanotech proves it can eradicate some of the most notorious and potentially deadly bacteria in the world. Developed by the University of South Australia and [...]
