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
GHCE Concept
From the preface of the book Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artificial Intelligence, Edited by Frank Boehm: Since the publication of my first book (Nanomedical Device and Systems [...]
Human Bodies Are Producing Two Billion Tons of CO2 a Year
A new study reveals that the amount of carbon dioxide produced by human metabolism has increased dramatically over three decades. The carbon dioxide produced by human bodies as they convert food into energy increased [...]
A Hidden DNA Mechanism Could Explain How 20% of Human Cancers Develop
Researchers have identified an unexpected molecular vulnerability in cancers carrying BAF mutations. Mutations found in roughly 20% of human cancers may promote tumor growth by changing how DNA is organized inside cells. Researchers have [...]
Ebola kills over 5,300 in fastest-growing outbreak on record
Africa’s latest Ebola outbreak has killed nearly 5,400 people, the vast majority of them in the Democratic Republic of Congo (DRC), according to the continent’s top health agency. Africa Centres for Disease Control and [...]
China makes early progress in using sound waves to stimulate damaged brains
Chinese researchers are testing whether focused ultrasound can help restore consciousness in patients with severe brain injuries, adding to a growing international effort to use sound waves to stimulate deep brain structures without surgery. [...]
Micro-drones fly through the body thanks to ultrasound
At the EPFL, micro-drones have been developed that can be moved without a motor or battery.No motors, no batteries, no electronics on board, just small cavities that convert sound waves into thrust: this is [...]
A Single Enzyme Could Hold the Key to Treating a Devastating Brain Disorder
Blocking an enzyme’s production restored brain growth and healthy behaviors in mice engineered to develop Angelman syndrome, pointing to a possible treatment target. Children with Angelman syndrome begin to show difficulties with thinking and [...]
Scientists Develop a Clever New Way To Kill Cancer Cells From the Inside
Scientists have developed an experimental strategy that exploits a chemical byproduct of cancer cells to produce anticancer drugs directly inside them. Scientists in Japan have developed an experimental method that uses a chemical produced [...]
Our books are available worldwide!
Online Sellers other than Amazon, Routledge, and IOPP Indigo Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artifcial Intelligence Global Health Care Equivalency In The Age Of Nanotechnology, Nanomedicine And Artificial [...]
After only a short training, people in a coma managed to send targeted signals
Researchers have succeeded in communicating with brain-injured patients who are unconscious. They see enormous potential in this for future treatments. Patients who lie motionless in bed after a severe brain injury and do not [...]
MIT Scientists Reprogram Immune Cells Inside the Body To Destroy Cancer
Natural killer cells reprogrammed inside mice eliminated lymphoma tumors and helped damaged livers heal, though whether this approach could help people with cancer or autoimmune disease remains unknown. To make a cancer treatment from [...]
Melanoma mRNA Vaccine Shows Promise in Preventing Disease Recurrence
Key takeaways: Phase 3 trial finds personalized intismeran plus pembrolizumab may better prevent high-risk melanoma recurrence after surgery The trial enrolled 1,137 patients and builds on phase 2 results showing about half the recurrence [...]
Scientists Discover a Powerful New Weapon Against a Dangerous Gut Infection
The promise of an experimental treatment for C. difficile gut infections lies partly in the bacteria it leaves alive, according to early laboratory and mouse research. Broad-spectrum antibiotics can disrupt the gut’s microbial community, [...]
Your Bones May Hold a Hidden Clue to Blood Cancer Survival
For people with blood cancers called myelodysplastic syndromes, osteoporosis may hold an overlooked clue to survival, a three-year observational study suggests. In blood cancers that develop in the bone marrow, an important clue to [...]
Researchers Discover What Reading for Pleasure May Be Doing to Your Brain
Reading for pleasure may offer surprising benefits for the brain, with research linking the habit to better mental health, stronger cognitive abilities, and a lower risk of dementia. Reading for pleasure may do far [...]
Scientists Discover a Hidden Trigger That Keeps Inflammation Alive
Inflammation persists after proteins detach from immune receptors, revealing a potential target for autoimmune treatments. Since a Nobel Prize-winning discovery in the 1990s identified molecules called Toll-like Receptors as the guardians of the human [...]
