Lifeboat Foundation

The CRISPR-Cas9 gene editing system is an extremely powerful tool, but there are still a few kinks to iron out. One of the main problems is off-target edits, which can have serious consequences. Now, researchers have found a particular mutation of the CRISPR enzyme that’s almost 100 times more precise than the most commonly used one.

CRISPR gene-editing is based on a bacterial defense system, in which the bugs use a particular enzyme to snip out a section of a pathogen’s DNA and store it for future reference. Next time that pathogen is encountered, the system will recognize it and be better equipped to fight it off.

Scientists managed to co-opt this system as a handy genetic engineering tool. CRISPR-Cas9 uses this mechanism to scour a target’s genome for a specific sequence of DNA – say one that could cause disease – then cut it out, sometimes replacing it with a more beneficial sequence.

The solution was to split the protein into two harmless halves. Liu’s team, led by graduate student Beverly Mok, used 3D imaging data from the Mougous lab to work out how to divide the protein into two pieces. Each piece did nothing on its own, but when reunited, they reconstituted the protein’s full activity. The team fused each deaminase half to customizable DNA-targeting proteins that did not require guide RNAs. Those proteins bound to specific stretches of DNA, bringing the two halves of the deaminase together. That let the molecule regain its function and work as a precision gene editor—but only once it was correctly positioned.

Liu’s team used the technology to make precise changes to specific mitochondrial genes. Then, Mootha’s lab, which focuses on mitochondrial biology, ran tests to see whether the edits had the intended effect. “You could imagine that if you’re introducing editing machinery into the mitochondria, you might accidentally cause some sort of a catastrophe,” Mootha said. “But it was very clean.” The entire mitochondrion functioned well, except for the one part the scientists intentionally edited, he explained.

This mitochondrial base editor is just the beginning, Mougous suggested. It can change one of the four DNA letters into another. He hopes to find additional deaminases that he and Liu can develop into editors able to make other mitochondrial DNA alterations. Such tools could enable new strategies for treating mitochondrial diseases, as well as help scientists to model diseases and aid in drug testing. “The ability to precisely install or correct pathogenic mutations could accelerate the modeling of diseases caused by mtDNA mutations, facilitate preclinical drug candidate testing, and potentially enable therapeutic approaches that directly correct pathogenic mtDNA mutations,” the authors noted. “Bacterial genomes contain various uncharacterized deaminases, raising the possibility that some may possess unique activities that enable new genome-editing capabilities.”

Various diseases of the digestive tract, for example severe intestinal inflammation in humans, are closely linked to disturbances in the natural mobility of the intestine. What role the microbiome—i.e. the natural microbial community colonizing the digestive tract—plays in these rhythmic contractions of the intestine, also known as peristalsis, is currently the subject of intensive research. It is particularly unclear how the contractions are controlled and how the cells of the nervous system, that act as pacemakers, function together with the microorganisms.

A research team from the Cell and Developmental Biology group at Kiel University has now succeeded in demonstrating for the first time, using the freshwater polyp Hydra as an example, that phylogenetically old neurons and bacteria actually communicate directly with each other. Surprisingly, they discovered that the nerve cells are able to cross-talk with the microorganisms via immune receptors, i.e., to some extent with the mechanisms of the immune system.

On this basis, the scientists of the Collaborative Research Center (CRC) 1182 “Origin and Function of Metaorganisms” formulated the hypothesis that the nervous system has not only taken over sensory and motor functions from the onset of evolution, but is also responsible for communication with the microbes. The Kiel researchers around Professor Thomas Bosch published their results together with international colleagues today in the journal Proceedings of the National Academy of Sciences (PNAS).

Canada’s highest court has issued a ruling today upholding a federal law preventing third parties, such as employers and insurance companies, from demanding genetic information from individuals.

In a 5–4 decision, the Supreme Court of Canada has decided the Genetic Non-Discrimination Act is a constitutional exercise of federal powers.

Most cells in your body come with two genetic libraries; one in the nucleus, and the other inside structures called mitochondria — also known as the ‘powerhouses of the cell’.

Until now, we’ve only had a way to make changes to one.

A combined effort by several research teams in the US has led to a process that could one day allow us to modify the instructions making up the cell’s ‘other’ genome, and potentially treat a range of conditions that affect how we power our bodies.

A bacterial toxin cracks open door to new precision-editing tool for DNA in mitochondria.

Look deep inside our cells, and you’ll find that each has an identical genome –a complete set of genes that provides the instructions for our cells’ form and function.

But if each blueprint is identical, why does an eye cell look and act differently than a skin cell or brain cell? How does a stem cell—the raw material with which our organ and tissue cells are made—know what to become?

In a study published July 8, University of Colorado Boulder researchers come one step closer to answering that fundamental question, concluding that the molecular messenger RNA (ribonucleic acid) plays an indispensable role in cell differentiation, serving as a bridge between our genes and the so-called “epigenetic” machinery that turns them on and off.

Tessera Therapeutics is developing a new class of gene editors capable of precisely plugging in long stretches of DNA—something that Crispr can’t do.

The Genome Aggregation Database has collected 15,708 genomes and 125,748 exomes (the protein-coding part of the genome) to help shed light on how genetic mutations can lead to disease. Dr Daniel MacArthur, scientific lead of the gnomAD Project, explains how the project started, how they collect the data and what they hope to achieve.