Nasal Spray Blocks Covid-19 and Other Viruses

Scientists at the University of California, Berkeley, have created a new COVID-19 therapeutic that could one day make treating SARS-CoV-2 infections as easy as using a nasal spray for allergies. The therapeutic uses short snippets of synthetic DNA to gum up the genetic machinery that allows SARS-CoV-2 to replicate within the body.

In a new study published online in the journal Nature Communications, the team shows that these short snippets, called antisense oligonucleotides (ASOs), are highly effective at preventing the virus from replicating in human cells. When administered in the nose, these ASOs are also effective at preventing and treating COVID-19 infection in mice and hamsters.

Vaccines are making a huge difference, but vaccines are not universal, and there is still a tremendous need for other approaches,” said Anders Näär, a professor of metabolic biology in the Department of Nutritional Sciences and Toxicology (NST) at UC Berkeley and senior author of the paper. “A nasal spray that is cheaply available everywhere and that could prevent someone from getting infected or prevent serious disease could be immensely helpful.”

Because the ASO treatment targets a portion of the viral genome that is highly conserved among different variants, it is effective against all SARS-CoV-2variants of concern” in human cells and in animal models. It is also chemically stable and relatively inexpensive to produce at large scale, making it ideal for treating COVID-19 infections in areas of the world that do not have access to electricity or refrigeration.

If the treatment proves to be safe and effective in humans, the ASO technology could be readily modified to target other RNA viruses. The research team is already searching for a way to use this to disrupt influenza viruses, which also have pandemic potential.

If we can design ASOs that target entire viral families, then when a new pandemic emerges, as long as we know which family the virus belongs to, we could use the nasally delivered ASOs to suppress the pandemic in its early stages,” said study first author Chi Zhu, a postdoctoral scholar in NST at UC Berkeley. “That’s the beauty of this new therapeutic.”

Source: https://news.berkeley.edu/

Can Humans Become Immortal?

Long life, de-aging, and immortality are some of the concepts that humans keep fiddling with. But, so far, there have been no answers that could unlock the secret of immortality, if it exists. Scientists have now turned for answers to the immortal jellyfish, a creature capable of repeatedly reverting into a younger state.

Spanish researchers have managed to decipher the genome of the immortal jellyfishTurritopsis dohrnii, and have defined various genomic keys that contribute to extending its longevity to the point of avoiding its death. Led by Dr. Carlos López-Otín of the University of Oviedo, the team mapped the genetic sequence of the unique jellyfish in hopes of unearthing the secret to their unique longevity and finding new clues to human aging. The study has been published in the Proceedings of the National Academy of Sciences. They sequenced Turritopsis dohrnii, together with that of its sister Turritopsis rubra to identify genes that are amplified or have different variant characteristics between the two.Turritopsis rubra is a close genetic cousin that lacks the ability to rejuvenate after sexual reproduction. They unraveled that T. dohrnii has variations in its genome that may make it better at copying and repairing DNA and they appear to be better at maintaining the ends of chromosomes called telomeres. The telomere length has been shown to shorten with age in humans.

Rather than having a single key to rejuvenation and immortality, the various mechanisms found in our work would act synergistically as a whole, thus orchestrating the process to ensure the successful rejuvenation of the immortal jellyfish,” Maria Pascual-Torner, first author of the article said in a statement. ”

Like other types of jellyfish, the T. dohrnii goes through a two-part life cycle, living on the sea floor during an asexual phase, where its chief role is to stay alive during times of food scarcity. When conditions are right, jellyfish reproduce sexually. Although many types of jellyfish have some capacity to reverse aging and revert to a larval stage, most lose this ability once they reach sexual maturity, the authors wrote. Not so for T. dohrnii.

Meanwhile, Carlos López-Otín, professor of Biochemistry and Molecular Biology at the Asturian university said, “This work does not pursue the search for strategies to achieve the dreams of human immortality that some announce, but to understand the keys and limits of the fascinating cellular plasticity that allows some organisms to be able to travel back in time. From this knowledge, we hope to find better answers to the numerous diseases associated with aging that overwhelm us today“.

Source: https://www.indiatoday.in/

CRISPR to Boost Tomatoes’ Vitamin D Levels

By making a few genetic tweaks using CRISPR technology, scientists have designed a special sun-dried tomato packed to the leaves with vitamin D. The flesh and peel of the fruit were genetically engineered to contain the same vitamin D levels as two eggs or 28 grams of tuna, both of which are currently recommended sources of the vital nutrient.

Researchers used gene editing to turn off a specific molecule in the plant’s genome which increased provitamin D3 in both the fruit and leaves of tomato plants. It was then converted to vitamin D3 through exposure to UVB lightVitamin D is created in our bodies after skin’s exposure to UVB light, but the major source is food. This new biofortified crop could help millions of people with vitamin D insufficiency, a growing issue linked to higher risk of cancer, dementia, and many leading causes of mortality. Studies have also shown that vitamin D insufficiency is linked to increased severity of infection by Covid-19.

Tomatoes naturally contain one of the building blocks of vitamin D3, called provitamin D3 or 7-dehydrocholesterol (7-DHC), in their leaves at very low levels. Provitamin D3, does not normally accumulate in ripe tomato fruits. Researchers in Professor Cathie Martin’s group at the John Innes Centre (in UK) used CRISPR-Cas9 gene editing to make revisions to the genetic code of tomato plants so that provitamin D3 accumulates in the tomato fruit. The leaves of the edited plants contained up to 600 ug of provitamin D3 per gram of dry weight. The recommended daily intake of vitamin d is 10 ug for adults. When growing tomatoes leaves are usually waste material, but those of the edited plants could be used for the manufacture of vegan-friendly vitamin D3 supplements, or for food fortification.

We’ve shown that you can biofortify tomatoes with provitamin D3 using gene editing, which means tomatoes could be developed as a plant-based, sustainable source of vitamin D3,” said Professor Cathie Martin, corresponding author of the study which appears in Nature Plants. “Forty percent of Europeans have vitamin D insufficiency and so do one billion people world-wide. We are not only addressing a huge health problem, but are helping producers, because tomato leaves which currently go to waste, could be used to make supplements from the gene-edited lines.”

Previous research has studied the biochemical pathway of how 7-DHC is used in the fruit to make molecules and found that a particular enzyme Sl7-DR2 is responsible for converting this into other molecules. To take advantage of this the researchers used CRISPR-Cas 9 to switch off this Sl7-DR2 enzyme in tomato so that the 7DHC accumulates in the tomato fruit. The researchers then tested whether the 7-DHC in the edited plants could be converted to vitamin D3 by shining UVB light on leaves.

After treatment with UVB light to turn the 7-DHC into Vitamin D3, one tomato contained the equivalent levels of vitamin D as two medium sized eggs or 28g tuna – which are both recommended dietary sources of vitamin D. The study says that vitamin D in ripe fruit might be increased further by extended exposure to UVB, for example during sun-drying.

Source: https://www.jic.ac.uk/

How to ‘Time Jump’ Skin Cells

Research from the Babraham Institute has developed a method to “time jump” human skin cells by 30 years, turning back the aging clock for cells without losing their specialized function. Work by researchers in the Institute’s Epigenetics research program has been able to partly restore the function of older cells, as well as rejuvenating the molecular measures of biological age. The research is published today in the journal eLife, and while this topic is still at an early stage of exploration, it could revolutionize regenerative medicine.

As we age, our cells‘ ability to function declines and the  accumulates marks of aging. Regenerative biology aims to repair or replace cells including old ones. One of the most important tools in regenerative biology is our ability to createinducedstem cells. The process is a result of several steps, each erasing some of the marks that make cells specialized. In theory, these stem cells have the potential to become any cell type, but scientists aren’t yet able to reliably recreate the conditions to re-differentiate stem cells into all cell types.

The new method, based on the Nobel Prize-winning technique scientists use to make stem cells, overcomes the problem of entirely erasing cell identity by halting reprogramming part of the way through the process. This allowed researchers to find the precise balance between reprogramming cells, making them biologically younger, while still being able to regain their specialized cell function.

In 2007, Shinya Yamanaka was the first scientist to turn normal cells, which have a specific function, into  which have the special ability to develop into any cell type. The full process of stem cell reprogramming takes around 50 days using four key molecules called the Yamanaka factors. The new method, called “maturation phase transient reprogramming,” exposes cells to Yamanaka factors for just 13 days. At this point, age-related changes are removed and the cells have temporarily lost their identity. The partly reprogrammed cells were given time to grow under normal conditions, to observe whether their specific skin cell function returned. Genome analysis showed that cells had regained markers characteristic of  (fibroblasts), and this was confirmed by observing collagen production in the reprogrammed cells.

Young fibroblasts in the first image, the two are after 10 days, on the right with treatment, the last two are after 13 days, right with treatment. Red shows collagen production which has been restored

To show that the cells had been rejuvenated, the researchers looked for changes in the hallmarks of aging. As explained by Dr. Diljeet Gill, a postdoc in Wolf Reik’s lab at the Institute who conducted the work as a Ph.D. student, “Our understanding of aging on a molecular level has progressed over the last decade, giving rise to techniques that allow researchers to measure age-related biological changes in human cells. We were able to apply this to our experiment to determine the extent of reprogramming our new method achieved.”

Source: https://phys.org/

Blood iron levels could be key to slowing ageing

Genes linked to ageing that could help explain why some people age at different rates to others have been identified by scientists. The international study using genetic data from more than a million people suggests that maintaining healthy levels of iron in the blood could be a key to ageing better and living longerThe findings could accelerate the development of drugs to reduce age-related diseases, extend healthy years of life and increase the chances of living to old age free of disease, the researchers say.

Scientists from the University of Edinburgh and the Max Planck Institute for Biology of Ageing in Germany focused on three measures linked to biological ageinglifespan, years of life lived free of disease (healthspan), and being extremely long–lived (longevity). Biological ageing – the rate at which our bodies decline over timevaries between people and drives the world’s most fatal diseases, including heart disease, dementia and cancers.

The researchers pooled information from three public datasets to enable an analysis in unprecedented detail. The combined dataset was equivalent to studying 1.75 million lifespans or more than 60,000 extremely long-lived people. The team pinpointed ten regions of the genome linked to long lifespan, healthspan and longevity. They also found that gene sets linked to iron were overrepresented in their analysis of all three measures of ageing.

Source: https://www.thebrighterside.news/

3D Mapping of Coronavirus Genome

The novel coronavirus uses structures within its RNA to infect cells. Scientists have now identified these configurations, generating the most comprehensive atlas to date of SARS-CoV-2’s genome. Although contained in a long, noodle-like molecule, the new coronavirus’s genome looks nothing like wet spaghetti. Instead, it folds into stems, coils, and cloverleafs that evoke molecular origami.

A team led by RNA scientist Anna Marie Pyle has now made the most comprehensive map to date of these genomic structures. In two preprints posted in July 2020 to bioRxiv.org, Pyle’s team mapped structures across the entire RNA genome of the coronavirus SARS-CoV-2, using living cells and computational analyses.

SARS-CoV-2 relies on its unique RNA structures to infect people and cause the illness COVID-19. But these structures’ contribution to infection and disease is often underappreciated, even among scientists, says Pyle, a Howard Hughes Medical Institute Investigator at Yale University.

Colorized scanning electron micrograph of a cell (blue) heavily infected with SARS-CoV-2 virus particles (red), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland

The general wisdom is that if we just focus on the proteins encoded in the virus’s genome, we’ll understand how SARS-CoV-2 works,” Pyle says. “But for these types of viruses, RNA structures in the genome can influence their ability to function as much as encoded proteins.”

Researchers can now begin to tease out just how these structures aid the virus—information that could ultimately lead to new treatments for COVID-19. Once scientists have identified RNA structures that carry out key tasks, for instance, it may be possible to devise ways to disrupt them—and interfere with infection.

Source: https://www.hhmi.org/
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https://phys.org/

Coronavirus Vaccine: When?

Researchers around the world are developing more than 165 vaccines against the coronavirus, and 27 vaccines are in human trials. Vaccines typically require years of research and testing before reaching the clinic, but scientists are racing to produce a safe and  effective vaccine by next year. But it is likeky that before the end of the summer we will know if one vaccine, at least, is efficient.

Work began in January with the deciphering of the genome. The first vaccine safety trials in humans started in March, but the road ahead remains uncertain. Some trials will fail, and others may end without a clear result. But a few may succeed in stimulating the immune system to produce effective antibodies against the virus.

Check the status of all the vaccines that have reached trials in humans, along with a selection of promising vaccines still being tested in cells or animals.

Source: https://www.nytimes.com/

How To Substantially Lower LDL Cholesterol Levels

Verve Therapeutics, a next-generation cardiovascular company, today announced the presentation of new preclinical proof-of-concept data in non-human primates that demonstrate the successful use of base editing to turn off a gene in the liver and thereby lower blood levels of either LDL cholesterol or triglyceride-rich lipoproteins, two factors leading to coronary atherosclerosis. Verve is developing one-time gene editing medicines that safely edit the adult human genome and mimic naturally-occurring cardioprotective variants to permanently knock out cholesterol-raising genes in the liver and treat coronary heart disease. The data were presented at the International Society for Stem Cell Research (ISSCR) 2020 Virtual Annual Meeting.

In a keynote address titled, “From reading the genome for risk to rewriting it for health,” Sekar Kathiresan, M.D., co-founder and chief executive officer of Verve Therapeutics, presented the results of recent studies utilizing adenine base editing (ABE) technology, licensed from Beam Therapeutics, in which substantial lowering of plasma LDL cholesterol or triglycerides was successfully demonstrated in non-human primates. Base editing is a gene editing technology developed to enable precise and permanent rewriting of a single DNA letter in the genome.

At Verve, our goal is to develop medicines, given once in life, that precisely edit targeted genes in the liver to permanently reduce LDL cholesterol and triglyceride levels in adults with coronary heart disease, the leading cause of death in the U.S. and worldwide,” said Dr. Kathiresan. “These proof-of-concept data, which to the best of our knowledge represent the first successful application of the base editing technology in non-human primates, show that we can safely edit the primate genome at highly efficacious levels to significantly lower blood LDL cholesterol and triglycerides. The findings are very encouraging and add to our growing body of evidence in using both base editing and CRISPR-Cas9 in vivo against various gene targets. We expect to choose a lead program by year-end 2020 with the goal of initiating human clinical studies within the next three years.”

The studies were conducted in a total of 14 non-human primates and evaluated in vivo liver base editing to turn off proprotein convertase subtilisin/kexin type 9 (PCSK9), a gene whose protein product elevates blood LDL cholesterol or angiopoietin-like protein 3 (ANGPTL3), a gene whose protein product elevates blood triglyceride-rich lipoproteins. Verve’s proprietary drug product consisting of the ABE mRNA and an optimized guide RNA packaged in an engineered lipid nanoparticle was delivered through a single intravenous infusion. Across two separate studies, seven animals were treated with the drug product targeting the PCSK9 gene and seven additional animals with the drug product targeting the ANGPTL3 gene.

Whole liver editing, blood protein and lipid levels were measured at two weeks and compared to baseline. The program targeting PCSK9 showed an average of 67% whole liver PCSK9 editing, which translated into an 89% reduction in plasma PCSK9 protein and resulted in a 59% reduction in blood LDL cholesterol levels. The program targeting ANGPTL3 showed an average of 60% whole liver ANGPTL3 editing, which translated into a 95% reduction in plasma ANGPTL3 protein and resulted in a 64% reduction in blood triglyceride levels and 19% reduction in LDL cholesterol levels.

Source: https://www.vervetx.com/

Breakthrough Against COVID-19

A team of scientists from Stanford University is working with researchers at the Molecular Foundry, a nanoscience user facility located at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), to develop a gene-targeting, antiviral agent against COVID-19. Last year, Stanley Qi, an assistant professor in the departments of bioengineering, and chemical and systems biology at Stanford University and his team had begun working on a technique called PAC-MAN – or Prophylactic Antiviral CRISPR in human cells – that uses the gene-editing tool CRISPR to fight influenza.

But that all changed in January, when news of the COVID-19 pandemic emerged. Qi and his team were suddenly confronted with a mysterious new virus for which no one had a clear solution.

Lipitoids, which self-assemble with DNA and RNA, can serve as cellular delivery systems for antiviral therapies that could prevent COVID-19 and other coronavirus infections.

So we thought, ‘Why don’t we try using our PAC-MAN technology to fight it?’” said Qi.

Since late March, Qi and his team have been collaborating with a group led by Michael Connolly, a principal scientific engineering associate in the Biological Nanostructures Facility at Berkeley Lab’s Molecular Foundry, to develop a system that delivers PAC-MAN into the cells of a patient.

Like all CRISPR systems, PAC-MAN is composed of an enzyme – in this case, the virus-killing enzyme Cas13 – and a strand of guide RNA, which commands Cas13 to destroy specific nucleotide sequences in the coronavirus’s genome. By scrambling the virus’s genetic code, PAC-MAN could neutralize the coronavirus and stop it from replicating inside cells.

Qi said that the key challenge to translating PAC-MAN from a molecular tool into an anti-COVID-19 therapy is finding an effective way to deliver it into lung cells. When SARS-CoV-2, the coronavirus that causes COVID-19, invades the lungs, the air sacs in an infected person can become inflamed and fill with fluid, hijacking a patient’s ability to breathe.

But my lab doesn’t work on delivery methods,” he said. So on March 14, they published a preprint of their paper, and even tweeted, in the hopes of catching the eye of a potential collaborator with expertise in cellular delivery techniques. Soon after, they learned of Connolly’s work on synthetic molecules called lipitoids at the Molecular Foundry. Lipitoids are a type of synthetic peptide mimic known as a “peptoid” first discovered 20 years ago by Connolly’s mentor Ron Zuckermann. In the decades since, Connolly and Zuckermann have worked to develop peptoid delivery molecules such as lipitoids. And in collaboration with Molecular Foundry users, they have demonstrated lipitoids’ effectiveness in the delivery of DNA and RNA to a wide variety of cell lines.

Today, researchers studying lipitoids for potential therapeutic applications have shown that these materials are nontoxic to the body and can deliver nucleotides by encapsulating them in tiny nanoparticles just one billionth of a meter wide – the size of a virus. Now Qi hopes to add his CRISPR-based COVID-19 therapy to the Molecular Foundry’s growing body of lipitoid delivery systems.

Source: https://newscenter.lbl.gov/

New Biosensor Measures The Concentration Of Covid-19 In The Air

A team of researchers from Empa, ETH Zurich and Zurich University Hospital has succeeded in developing a novel sensor for detecting the new coronavirus. In future it could be used to measure the concentration of the virus in the environment – for example in places where there are many people or in hospital ventilation systems.

Jing Wang and his team at Empa and ETH Zurich usually work on measuring, analyzing and reducing airborne pollutants such as aerosols and artificially produced nanoparticles. However, the challenge the whole world is currently facing is also changing the goals and strategies in the research laboratories. The new focus: a sensor that can quickly and reliably detect SARS-CoV-2 – the new coronavirus.

But the idea is not quite so far removed from the group’s previous research work: even before the COVID-19 began to spread, first in China and then around the world, Wang and his colleagues were researching sensors that could detect bacteria and viruses in the air. The sensor will not necessarily replace the established laboratory tests, but could be used as an alternative method for clinical diagnosis, and more prominently to measure the virus concentration in the air in real time: For example, in busy places like train stations or hospitals.

Fast and reliable tests for the new coronavirus are urgently needed to bring the pandemic under control as soon as possible. Most laboratories use a molecular method called reverse transcription polymerase chain reaction, or RT-PCR for short, to detect viruses in respiratory infections. This is well established and can detect even tiny amount of viruses – but at the same time it can be time consuming and prone to error.

Jing Wang and his team have developed an alternative test method in the form of an optical biosensor. The sensor combines two different effects to detect the virus safely and reliably: an optical and a thermal one.

The sensor uses an optical and a thermal effect to detect the COVID-19-Virus safely and reliably

The sensor is based on tiny structures of gold, so-called gold nanoislands, on a glass substrate. Artificially produced DNA receptors that match specific RNA sequences of the SARS-CoV-2 are grafted onto the nanoislands. The coronavirus is a so-called RNA virus: Its genome does not consist of a DNA double strand as in living organisms, but of a single RNA strand. The receptors on the sensor are therefore the complementary sequences to the virus’ unique RNA sequences, which can reliably identify the virus.

The technology the researchers use for detection is called LSPR, short for localized surface plasmon resonance. This is an optical phenomenon that occurs in metallic nanostructures: When excited, they modulate the incident light in a specific wavelength range and create a plasmonic near-field around the nanostructure. When molecules bind to the surface, the local refractive index within the excited plasmonic near-field changes. An optical sensor located on the back of the sensor can be used to measure this change and thus determine whether the sample contains the RNA strands in question.

Source: https://www.empa.ch/