The Virus Trap

To date, there are no effective antidotes against most virus infections. An interdisciplinary research team at the Technical University of Munich (TUM) has now developed a new approach: they engulf and neutralize viruses with nano-capsules tailored from genetic material using the DNA origami method. The strategy has already been tested against hepatitis and adeno-associated viruses in cell cultures. It may also prove successful against corona viruses.

There are antibiotics against dangerous bacteria, but few antidotes to treat acute viral infections. Some infections can be prevented by vaccination but developing new vaccines is a long and laborious process.

Now an interdisciplinary research team from the Technical University of Munich, the Helmholtz Zentrum München and the Brandeis University (USA) is proposing a novel strategy for the treatment of acute viral infections: The team has developed nanostructures made of DNA, the substance that makes up our genetic material, that can trap viruses and render them harmless.

Lined on the inside with virus-binding molecules, nano shells made of DNA material bind viruses tightly and thus render them harmless.

Even before the new variant of the corona virus put the world on hold, Hendrik Dietz, Professor of Biomolecular Nanotechnology at the Physics Department of the Technical University of Munich, and his team were working on the construction of virus-sized objects that assemble themselves.

In 1962, the biologist Donald Caspar and the biophysicist Aaron Klug discovered the geometrical principles according to which the protein envelopes of viruses are built. Based on these geometric specifications, the team around Hendrik Dietz at the Technical University of Munich, supported by Seth Fraden and Michael Hagan from Brandeis University in the USA, developed a concept that made it possible to produce artificial hollow bodies the size of a virus.

In the summer of 2019, the team asked whether such hollow bodies could also be used as a kind of “virus trap”. If they were to be lined with virus-binding molecules on the inside, they should be able to bind viruses tightly and thus be able to take them out of circulation. For this, however, the hollow bodies would also have to have sufficiently large openings through which viruses can get into the shells.

None of the objects that we had built using DNA origami technology at that time would have been able to engulf a whole virus – they were simply too small,” says Hendrik Dietz in retrospect. “Building stable hollow bodies of this size was a huge challenge.”

Starting from the basic geometric shape of the icosahedron, an object made up of 20 triangular surfaces, the team decided to build the hollow bodies for the virus trap from three-dimensional, triangular plates. For the DNA plates to assemble into larger geometrical structures, the edges must be slightly beveled. The correct choice and positioning of binding points on the edges ensure that the panels self-assemble to the desired objects.

In this way, we can now program the shape and size of the desired objects using the exact shape of the triangular plates,” says Hendrik Dietz. “We can now produce objects with up to 180 subunits and achieve yields of up to 95 percent. The route there was, however, quite rocky, with many iterations.”

By varying the binding points on the edges of the triangles, the team’s scientists can not only create closed hollow spheres, but also spheres with openings or half-shells. These can then be used as virus traps.

Source: https://www.tum.de/

Reversal of Aging is Closer

The cure for aging has long been the Holy Grail of medicine. Emerging technologies, like the gene editing tool CRISPR, have opened the floodgates to what may be possible for the future of medical science. The key to slowing down aging, however, may lie in a simple and age-old technique. For the first time, Israeli scientists showed the reversal of aging in two key biological clocks in humans, by giving patients oxygen therapy in a pressurized chamber. The results appear in the journal Aging.

As you grow older and your cells continue to divide, sequences of DNA at the end of chromosomes, called telomeres, gradually become shorter. Once the telomeres become too short, the cell can no longer replicate and eventually dies. This isn’t necessarily a bad thing.

Telomere shortening can prevent rogue cancerous cells from multiplying uncontrollably, but unfortunately, this comes with the cost of genetic aging. These geriatric cells that can no longer divide are also known as senescent cells, which accumulate over the period of your life and are believed to be one of the leading causes of aging. In a clinical trial, 35 healthy adults aged 64 and older received 60 oxygen therapy sessions daily over the course of three months. The scientists collected the subjects’ blood samples prior to treatment, after the first and second months of the trial, and two weeks after the trial was over. None of the patients had any lifestyle, diet, or medication changes throughout the study, and yet their blood work showed significant increases in the telomere length of their cells and a decrease in the number of their senescent cells. This isn’t the first time doctors have put patients into pressurized oxygen chambers. Hyperbaric oxygen therapy (HBOT) has been used for almost a century to treat a number of illnesses, including decompression sickness in deep-sea divers and carbon monoxide poisoning.

The therapy involves breathing pure oxygen in a pressurized chamber, which causes blood and tissues in your body to become saturated with oxygen. Strangely enough, this can trigger similar physiological effects that occur when your body is starved of oxygen, known as hypoxia. While previous research shows these effects can stimulate your brain and increase your cognitive abilities, this is the first study to show the therapy may also reverse aging.

Since telomere shortening is considered the ‘Holy Grail’ of the biology of aging, many pharmacological and environmental interventions are being extensively explored in the hopes of enabling telomere elongation,” said study coauthor Shai Efrati, a professor at the Sackler School of Medicine at Tel Aviv University. The significant improvement of telomere length shown during and after these unique HBOT protocols provides the scientific community with a new foundation of understanding that aging can, indeed, be targeted and reversed at the basic cellular-biological level.

This also isn’t the first time scientists have claimed to reverse aging. Several studies using pharmacological drugs, such as danazol, have been shown to elongate telomeres. Additionally, lifestyle changes, including exercise and healthy diets, have been shown to have small effects on the growth of telomeres. “Until now, interventions such as lifestyle modifications and intense exercise were shown to have some inhibition effect on the expected telomere length shortening. However, what is remarkable to note in our study, is that in just three months of HBOT, we were able to achieve such significant telomere elongation—at rates far beyond any of the current available interventions or lifestyle modifications,” study coauthor Amir Hadanny, a neurosurgeon at the Sagol Center of Hyperbaric Medicine and Research in Israel, explained in the press release.

Source: https://www.popularmechanics.com/

RNA Could Be The Future of Cancer Treatment

Cells are the basic building blocks of all living things. So, in order to treat or cure almost any disease or condition – including cancer – you first need to have a fundamental understanding of cell biology. While researchers have a pretty good understanding of what each component of a cell does, there are still things we don’t know about them – including the role that some RNAs molecules play in a cell.

Finding the answer to this may be key in developing further cancer treatments, which is what our research has sought to uncover. Three types of molecules carry information in a cell, and each of these molecules performs its own important function. The first is DNA, which contains hard-wired genetic information (like a book of instructions). . The second, RNA, is a temporary copy of one particular instruction that is derived from DNA. Last are the proteins produced thanks to the information provided by the RNA. These proteins are the “workhorses” of the cells, which perform specific functions, such as helping cells move, reproduce, and generate energy.

In line with this model, RNA has long been seen as nothing more than an intermediary between DNA and proteins. But researchers are starting to discover that RNA is much more than an intermediary. In fact, this overlooked molecule may hold the secret to cancer progression. The scientists group recently discovered a new type of RNA that drives cancer progression without producing any protein. We think that this type of discovery may pave the way for an entirely new way of targeting cancer cells. But to understand how this is possible, it’s first important to know the different types of RNA we have in our body. Only about 1% of DNA is copied into RNAs that make proteins. Other RNAs help the production of proteins. The rest (known as non-coding RNAs) were long assumed to serve no function in the human body. But recent studies are challenging these assumptions, showing these “uselessRNAs actually performvery specific purpose. In fact, these “non-coding” RNAs regulate the functions of many genes, thereby controlling key aspects of the cells’ lives (such as their ability to move around).

The most abundant type of non-coding RNAs are long non-coding RNAs (lncRNAs). These are long molecules which interact with many different molecules in the cell. And, as researchers have now discovered, these complex structures allow many different functions to take place between cells.

For example, some lncRNAsgrab” different proteins and gather them to work in a specific cellular space – such as the same gene segment. This function is essential for controlling the inactivation of some genes during development.

Source: https://nationalinterest.org/

Reversible Gene Editing

The gene-editing system, CRISPR-Cas9, is truly revolutionizing medicine: in the future, it may help us eradicate ailments from sickle cell, cancer, and even blindness. While this system allows scientists to make changes to DNA, the changes are permanent. On the one hand, this is useful, because it could potentially cure genetic diseases without requiring a lifetime of treatment. The downside is that unintended consequences of the edits are difficult to fix — especially “off-targetedits, where CRISPR changes the wrong stretch of DNA. This is a huge concern for the scientific community — no one wants to be responsible for genetic mutations that go awry.

But what if the changes were not permanent? What if we could simply turn CRISPR off whenever we wanted?  A team of researchers at MIT and UCSF has developed a new gene-editing system that they call “CRISPRoff.” According to the researchers, this system can change how specific genes behave, much like CRISPR, while leaving the DNA strand unaltered — and even better, these modifications are completely reversible.

The traditional CRISPR system invented in 2012 relies on a protein called Cas9, which is found in bacterial immune systems. Cas9 can target specific genes and cut the DNA strand, removing or replacing defective genes. The DNA then self-repairs and continues functioning after the gene has been removed. Because this system alters the DNA sequence, the changes are permanent, and even though CRISPR is one of the most accurate ways to change DNA, it can be difficult to ensure that the modification will always be limited to that one gene.

As beautiful as CRISPR-Cas9 is, it hands off the repair to natural cellular processes, which are complex and multifaceted,MIT‘s Jonathan Weissman and coauthor of the study, said in a press release. “It’s very hard to control the outcomes.”

CRISPRoff is a new kind of gene-editing technology that doesn’t modify the DNA sequence, but instead changes the way those sequences are read. With this system, scientists can silence or activate various genes by adding chemical tags onto the DNA strand, without making any permanent changes. The tags cause the DNA to become unreadable by the cell’s messenger RNA, the molecule responsible for carrying instructions from the DNA to make proteins.

Source: https://news.mit.edu/

Scribe Therapeutics change the genes responsible for causing diseases

Imagine being able to change the genes responsible for causing diseases. For Scribe Therapeutics, a gene-editing company that develops genetic medicines, this is no longer a dream but a reality. Scribe Therapeutics is one of several companies approaching genetic medicines through Crispr, the now-famous “molecular scissors” employed to cut and edit DNA. But the company is taking a new approach to leveraging Crispr technology. Instead of relying on wild-type or naturally occurring Crispr molecules such as Cas9, Scribe Therapeutics have built their own, highly-specialized varieties.

Founded by Jennifer Doudna, Benjamin Oakes, Brett Staahl, and David Savage, Scribe Therapeutics is creating an advanced platform for Crispr-based genetic medicine.

Crispr is changing how we think about treating diseases,” says co-founder, President, and CEO of Scribe Therapeutics, Benjamin Oakes. “When I finished my undergraduate degree, I shadowed doctors and realized we had no way to treat the underlying causes of diseases. This changed my career path to creating Crispr-based tools that can actually treat the underlying causes.”

Scribe Therapeutics has collaborated with Biogen to create Crispr-based genetic medicines for diseases such as amyotrophic lateral sclerosis (ALS). The company is also studying how to use adeno-associated virus (AAV) vectors to deliver Crispr components to the nervous system, eyes, and muscles. AAV vectors can deliver DNA to specific target cells for therapeutic uses.

Today, Scribe Therapeutics announced a $100 million Series B funding round that will help the company grow and expand. One of the key ways it stands out from other synthetic biology and gene-editing companies is through its approach to doing science. Other companies sometimes create tools without thinking about the problems they can solve, but Scribe Therapeutics is different. Instead of building technology in need of a solution, Scribe Therapeutics finds the problem first and creates the technology to fix it.

We face challenges head-on and continue to inspire people to try the hard things. You have to encourage fearlessness in science. If your experiment failed today, it doesn’t mean you’re a failure. You have to keep trying,” says Oakes.

Scribe Therapeutics‘ “Crispr by designplatform has custom-engineered millions of novel molecules specifically designed for therapeutic uses within the human body. For example, its X-editing (XE) technology is an engineered molecule that offers greater specificity, activity, and deliverability when used therapeutically.

Source: https://www.forbes.com/

Summer Sunlight Could Inactivate 90% of Coronavirus Particles in 30 minutes

A team of scientists is calling for greater research into how sunlight inactivates SARS-CoV-2 after realizing there’s a glaring discrepancy between the most recent theory and experimental results. UC Santa Barbara mechanical engineer Paolo Luzzatto-Fegiz and colleagues noticed the virus was inactivated as much as eight times faster in experiments than the most recent theoretical model predicted.

The theory assumes that inactivation works by having UVB hit the RNA of the virus, damaging it,” explained Luzzatto-Fegiz.

But the discrepancy suggests there’s something more going on than that, and figuring out what this is may be helpful for managing the virus.

UV light, or the ultraviolet part of the spectrum, is easily absorbed by certain nucleic acid bases in DNA and RNA, which can cause them to bond in ways that are hard to fix.

But not all UV light is the sameLonger UV waves, called UVA, don’t have quite enough energy to cause problems. It’s the mid-range UVB waves in sunlight that are primarily responsible for killing microbes and putting our own cells at risk of Sun damage.

Short-wave UVC radiation has been shown to be effective against viruses such as SARS-CoV-2, even while it’s still safely enveloped in human fluids.

But this type of UV doesn’t usually come into contact with Earth’s surface, thanks to the ozone layer.

UVC is great for hospitals,” said co-author and Oregon State University toxicologist Julie McMurry. “But in other environments – for instance, kitchens or subways – UVC would interact with the particulates to produce harmful ozone.”

In July 2020, an experimental study tested the effects of UV light on SARS-CoV-2 in simulated saliva. They recorded the virus was inactivated when exposed to simulated sunlight for between 10-20 minutes.

Natural sunlight may be effective as a disinfectant for contaminated nonporous materials,” Wood and colleagues concluded in the paper.

Luzzatto-Feigiz and team compared those results with a theory about how sunlight achieved this, which was published just a month later, and saw the math didn’t add up. his study found the SARS-CoV-2 virus was three times more sensitive to the UV in sunlight than influenza A, with 90 percent of the coronavirus‘s particles being inactivated after just half an hour of exposure to midday sunlight in summer.

By comparison, in winter light infectious particles could remain intact for days.

Source: https://www.news.ucsb.edu/
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https://www.sciencealert.com/

Artificial Cell Grows And Divides Like a Natural One

Five years ago, scientists created a single-celled synthetic organism that, with only 473 genes, was the simplest living cell ever known. However, this bacteria-like organism behaved strangely when growing and dividing, producing cells with wildly different shapes and sizes. Now, scientists have identified seven genes that can be added to tame the cells’ unruly nature, causing them to neatly divide into uniform orbs.

Identifying these genes is an important step toward engineering synthetic cells that do useful things. Such cells could act as small factories that produce drugs, foods and fuels; detect disease and produce drugs to treat it while living inside the body; and function as tiny computers. But to design and build a cell that does exactly what you want it to do, it helps to have a list of essential parts and know how they fit together.

We want to understand the fundamental design rules of life,” said Elizabeth Strychalski, a co-author on the study and leader of NIST’s Cellular Engineering Group. “If this cell can help us to discover and understand those rules, then we’re off to the races.”

Scientists at JCVI constructed the first cell with a synthetic genome in 2010. They didn’t build that cell completely from scratch. Instead, they started with cells from a very simple type of bacteria called a mycoplasma. They destroyed the DNA in those cells and replaced it with DNA that was designed on a computer and synthesized in a lab. This was the first organism in the history of life on Earth to have an entirely synthetic genome. They called it JCVI-syn1.0.

Since then, scientists have been working to strip that organism down to its minimum genetic components. The super-simple cell they created five years ago, dubbed JCVI-syn3.0, was perhaps too minimalist. The researchers have now added 19 genes back to this cell, including the seven needed for normal cell division, to create the new variant, JCVI-syn3A. This variant has fewer than 500 genes. To put that number in perspective, the E. coli bacteria that live in your gut have about 4,000 genes. A human cell has around 30,000.

This achievement, a collaboration between the J. Craig Venter Institute (JCVI), the National Institute of Standards and Technology (NIST) and the Massachusetts Institute of Technology (MIT) Center for Bits and Atoms, is described in the journal Cell.

Source: https://www.nist.gov/

New Blood Test Could Replace Biopsies

No one enjoys getting a biopsy, in which a tissue sample is surgically taken and analyzed in a lab for signs of disease, such as cancer. It’s not only unpleasant for the patient, but has clinical drawbacks: A biopsy doesn’t always extract the diseased tissue and isn’t helpful in detecting disease at early stages. These concerns have encouraged researchers to find less invasive and more accurate diagnostic methods. Prof. Nir Friedman and Ronen Sadeh of the Hebrew University of Jerusalem have developed a blood test that enables lab technicians to diagnose cancer and diseases of the heart and liver by identifying and determining the state of the dead cells throughout the body.

Millions of cells die every day and are replaced by new cells. When cells die, their DNA is fragmented. Some of these DNA fragments reach the blood and can be “read” by advanced DNA sequencing methods.

As a result of these scientific advancements, we understood that if this information is maintained within the DNA structure in the blood, we could use that data to determine the tissue source of dead cells and the genes that were active in those very cells. Based on those findings, we can uncover key details about the patient’s health,” Friedman said.

We are able to better understand why the cells died — whether it’s an infection or cancer — and based on that, be better positioned to determine how the disease is developing,” he said. Co-author Israa Sharkia added the simple blood test could “be administered often and quickly, allowing the medical staff involved to follow the presence or development of a disease more closely.”

A startup company, Senseera, has been established to pursue clinical testing of this innovative approach in partnership with major pharmaceutical companies.

The multi-author study published in Nature Biotechnology explains the test can even identify markers that may differentiate between patients with similar tumors, which could help physicians develop personalized treatments.

Source: https://www.zenger.news/

Katalin Kariko, RNA Hero, Future Nobel Prize

The development of the Pfizer-BioNTech coronavirus vaccine, the first approved jab in the West, is the crowning achievement of decades of work for Hungarian biochemist Katalin Kariko, who fled to the US from communist rule in the 1980s.

When trials found the Pfizer-BioNTech coronavirus vaccine to be safe and 95 percent effective in November, it was the crowning achievement of Katalin Kariko’s 40 years of research on the genetic code RNA (ribonucleic acid). Her first reaction was a sense of “redemption,” Kariko told The Daily Telegraph.

I was grabbing the air, I got so excited I was afraid that I might die or something,” she said from her home in Philadelphia. “When I am knocked down I know how to pick myself up, but I always enjoyed working… I imagined all of the diseases I could treat.”

Born in January 1955 in a Christian family in the town of Szolnok in central Hungary – a year before the doomed heroism of the uprising against the Soviet-backed communist regimeKariko grew up in nearby Kisujszellas on the Great Hungarian Plain, where her father was a butcher. Fascinated by science from a young age, Kariko began her career at the age of 23 at the University of Szeged’s Biological Research Centre, where she obtained her PhD.

It was there that she first developed her interest in RNA. But communist Hungary’s laboratories lacked resources, and in 1985 the university sacked her. Consequently, Kariko looked for work abroad, getting a job at Temple University in Philadelphia the same year. Hungarians were forbidden from taking money out of the country, so she sold the family car and hid the proceeds in her 2-year-old daughter’s teddy bear. “It was a one-way ticket,” she told Business Insider. “We didn’t know anybody.”

Not everything went as planned after Kariko’s escape from communism. At the end of the 1980s, the scientific community was focused on DNA, which was seen as the key to understanding how to develop treatments for diseases such as cancer. But Kariko’s main interest was RNA, the genetic code that gives cells instructions on how to make proteins.

At the time, research into RNA attracted criticism because the body’s immune system sees it as an intruder, meaning that it often provokes strong inflammatory reactions. In 1995, Kariko was about to be made a professor at the University of Pennsylvania, but instead she was consigned to the rank of researcher.

Usually, at that point, people just say goodbye and leave because it’s so horrible,” Kariko told medical publication Stat. She went through a cancer scare at the time, while her husband was stuck in Hungary trying to sort out visa issues. “I tried to imagine: Everything is here, and I just have to do better experiments,” she continued. Kariko was also on the receiving end of sexism, with colleagues asking her the name of her supervisor when she was running her own lab.

Kariko persisted in the face of these difficulties. “From outside, it seemed crazy, struggling, but I was happy in the lab,” she told Business Insider. “My husband always, even today, says, ‘This is entertainment for you.’ I don’t say that I go to work. It is like play.” Thanks to Kariko’s position at the University of Pennsylvania, she was able to send her daughter Susan Francia there for a quarter of the tuition costs. Francia won gold on the US rowing team in the 2008 and 2012 Olympics.

It was a serendipitous meeting in front of a photocopier in 1997 that turbocharged Kariko’s career. She met immunologist Drew Weissman, who was working on an HIV vaccine. They decided to collaborate to develop a way of allowing synthetic RNA to go unrecognised by the body’s immune system – an endeavour that succeeded to widespread acclaim in 2005. The duo continued their research and succeeded in placing RNA in lipid nanoparticles, a coating that prevents them from degrading too quickly and facilitates their entry into cells.

The researchers behind the Pfizer-BioNTech and Moderna jabs used these techniques to develop their vaccines.

Source: https://www.france24.com/

Base Editing Could Cure a Host of Genetic Diseases

Picture the familiar double helix of human DNA — a long, twisted ladder with 3 billion rungs on it, each made of a pair of genetic bases (A, T, C, and G). A mistake in just one base along that ladderan A where there should be a G — can be enough to cause a disease. In fact, researchers have linked over 31,000 different mistakes, known as “point mutations,” to human diseases. Now, an advanced form of gene therapy — called base editing — could make it possible to safely correct them.

Base editing is a type of gene editing technology, just like CRISPR. However, while CRISPR cuts through both strands of the DNA ladder to swap in different genes, a base editor makes precise changes to individual letters along the genome — a much less invasive kind of DNA surgery.

It’s like your spell-checker,” neuroscientist Jeffrey Holt said. “If you type the wrong letter, spell checker fixes it for you.” Base editing was first developed by Broad Institute researcher David Liu in 2016, and it’s not perfect — the best base editors still make off-target edits and aren’t 100%  efficient. However, the technique is more efficient than CRISPR and causes fewer errors, which has made it the focus of considerable research into correcting disease-causing point mutations.

Base editing is like your spell-checker. If you type the wrong letter, it fixes it for you,” explained Jeffrey Holt. Holt was part of a team that used base editing to partially restore the hearing of mice with a point mutation that causes deafness in people. Earlier in 2020, University of Illinois researchers used base editing to slow the progression of ALS in mice. More recently, Liu was part of a group that used base editing to correct the point mutation that causes progeria, a premature-aging syndrome, in mice. By changing a T to a C in a single gene, they were able to more than double the lifespan of mice with the disease.

There’s no guarantee that a therapy that works in mice will translate to humans (although gene editing is conceptually much simpler than drugs that rely on complex chemistry). To find out whether base editing can live up to its promise as a disease-curing technology, we need human studies — and now, one is just on the horizon.

On January 12, Massachusetts-based biotech company Verve Therapeutics announced the promising results of a study testing a base editing treatment for heterozygous familial hypercholesterolemia (HeFH), a genetic heart diseaseHeFH is fairly common, affecting about one in 500 people, and it causes consistently high levels of “badcholesterol (LDL-C) — that makes people with the disease susceptible to heart attacks or strokes at a relatively young age. In primates with HeFH, Verve used base editing to change an A to a G in a single gene. Within two weeks, the animals’ blood LDL-C levels had dropped by 59%. Six months later, they were still just as low.The treatment, dubbed “VERVE-101,” was well-tolerated, with no adverse effects reported.

When we started, we had no idea this would work,” Verve CEO Sekar Kathiresan said in a press release, adding, “It works, and we expect this to be durable for the lifetime of the animals.” Now, Verve wants to find out if VERVE-101 works in humans.

Source: https://www.freethink.com/