AI Tailors Artificial DNA

With the help of an AI, researchers at Chalmers University of Technology, Sweden, have succeeded in designing synthetic DNA that controls the cells’ protein production. The technology can contribute to the development and production of vaccines, drugs for severe diseases, as well as alternative food proteins much faster and at significantly lower costs than today.

How our genes are expressed is a process that is fundamental to the functionality of cells in all living organisms. Simply put, the genetic code in DNA is transcribed to the molecule messenger RNA (mRNA), which tells the cell’s factory which protein to produce and in which quantities.

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Personalized Skin Cancer Vaccine

Two major pharmaceutical companies are testing a personalized vaccine that might prevent the recurrence of a specific type of skin cancer. Moderna, one of the companies behind the COVID-19 vaccine, and Merck, an enterprise focused largely on oncology and preventative medicines, are teaming up to see if they can reduce the public’s risk of re-developing the deadliest form of skin cancer: melanoma.

The vaccine essentially combines two medical technologies: the mRNA vaccine and Merck’s Keytruda. As with the COVID-19 vaccine, mRNA shots don’t require an actual virus. Instead, they use a disease’s genetic code to “teach” the immune system to recognize and fight that particular illness. This makes it relatively easy and inexpensive for scientists to develop mRNA vaccines and edit them if a new form of the disease emerges. Keytruda, meanwhile, is a prescription medication that helps prevent melanoma from coming back after known cancer cells have been surgically removed.

Moderna and Merck are testing the feasibility of not only creating a two-in-one drug with both technologies but also customizing individual vaccines to suit their respective patients. Each vaccine is engineered to activate the patient’s immune system, which in turn deploys T cells (a type of white blood cell known to fight cancer) that go after the specific mutations of a patient’s tumor. Keytruda assists this effort by barring certain cell proteins from getting in the way of T cells’ intervention.

The experimental drug is currently in its second clinical trial out of three. The trial involves 157 participants with high-risk melanoma who just successfully underwent surgical removal. Some of the participants were given the personalized vaccine, while others were given Keytruda alone. Moderna and Merck will observe whether the participants’ melanoma returns over the span of approximately one year, with primary data expected at the end of this year.

If a vaccine preventing the recurrence of melanoma does in fact become commercially available, it could prevent more than 7,000 deaths per year in the US alone.

Source: https://www.extremetech.com/

Cancer-killing Virus Shrinks Tumours of A Third of the Patients

A new type of cancer therapy that uses a common virus to infect and destroy harmful cells is showing big promise in early  human trials, say UK scientists. One patient’s cancer vanished, while others saw their tumours shrink. The drug is a weakened form of the cold sore virusherpes simplex – that has been modified to kill tumours. Larger and longer studies will be needed, but experts say the injection might ultimately offer a lifeline to more people with advanced cancers.

Krzysztof Wojkowski, a 39-year-old builder from west London, is one of the patients who took part in the ongoing phase one safety trial, run by the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust. He was diagnosed in 2017 with cancer of the salivary glands, near the mouth. Despite surgery and other treatments at the time, his cancer continued to grow.

I was told there was no options left for me and I was receiving end-of-life care. It was devastating, so it was incredible to be given the chance to join the trial.” A short course of the virus therapy – which is a specially modified version of the herpes virus which normally causes cold sores – appears to have cleared his cancer. “I had injections every two weeks for five weeks which completely eradicated my cancer. I’ve been cancer-free for two years now.”

The injections, given directly into the tumour, attacks cancer in two ways – by invading the cancerous cells and making them burst, and by activating the immune system. About 40 patients have tried the treatment as part of the trial. Some were given the virus injection, called RP2, on its own. Others also received another cancer drug – called nivolumab – as well.

The findings, presented at a medical conference in Paris, France, show that three out of nine patients given RP2 only, which included Krzysztof, saw their tumours shrink.

Source: https://www.bbc.com/

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/

Revolutionary Cancer-Killing Virus Tested

Scientists have injected the first human patient with a new ‘cancer-killing virus‘ that has been shown to shrink solid tumours in animals. The virus, known as Vaxinia, has been genetically engineered to infect, replicate in and kill cancer cells, while sparing healthy cells. Tests on animals have shown it is able to reduce the size of colon, lung, breast, ovarian and pancreatic cancer tumours.

While other immunotherapies such as checkpoint inhibitors have been effective in certain cancers, patients often relapse and eventually stop responding to or develop resistance to this type of treatment, according to the researchers. In contrast, Vaxinia can prime the patient’s immune system and increase the level of a protein called PD-L1 in tumours, making immunotherapy more effective against cancerVaxinia, (full name CF33-hNIS VAXINIA), is a type of ‘oncolytic virus‘ – a virus found in nature that has been genetically modified specifically to fight cancer. It is being developed by Imugene Limited, a company specialising in novel therapies that activate the immune system against cancer.

Our previous research demonstrated that oncolytic viruses can stimulate the immune system to respond to and kill cancer, as well as stimulate the immune system to be more responsive to other immunotherapies, including checkpoint inhibitors,‘ said Daneng Li MD, principal investigator and assistant professor of City of Hope‘s Department of Medical Oncology & Therapeutics Research. ‘Now is the time to further enhance the power of immunotherapy, and we believe CF33-hNIS has the potential to improve outcomes for our patients in their battle with cancer.’

The Phase 1 clinical trial aims to recruit 100 cancer patients with metastatic or advanced solid tumours across approximately 10 trial sites in the United States and Australia. It is anticipated to run for approximately 24 months. Patients will begin by receiving a low dose of Vaxinia, either as an injection directly into tumours or intravenously. Once the safety of Vaxina has been demonstrated, some participants will also receive an immunotherapy drug called pembrolizumab, which improves the immune system’s ability to fight cancer-causing cells.

Interestingly, the same characteristics that eventually make cancer cells resistant to chemotherapy or radiation treatment actually enhance the success of oncolytic viruses, such as CF33-hNIS,’ said Yuman Fong MD, the Sangiacomo Family Chair in Surgical Oncology at City of Hope and the key developer of the genetically modified virus.

Source: https://www.cityofhope.org/
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Nano-Robots Injected into your Bloodstream to Fight Disease

What if there was a magical robot that could cure any disease? Don’t answer that. It’s a stupid question. Everyone knows there’s no one machine that could do that. But maybe a swarm made up of tens of thousands of tiny autonomous micro-bots could? That’s the premise laid out by proponents of nanobot medical technology. In science fiction, the big idea usually involves creating tiny metal robots via some sort of magic-adjacent miniaturization technology.

Luckily for us, the reality of nanobot tech is infinitely cooler. A team of researchers from Australia have developed a mind-blowing prototype that could work as a proof-of-concept for the future of medicine. Called “autonomous molecular machines,” the new nanotechnology eschews the traditional visage of microscopic metal automatons in favor of a more natural approach.

Inspired by biology, we design and synthesize a DNA origami receptor that exploits multivalent interactions to form stable complexes that are also capable of rapid subunit exchange”, explained the researchers. “DNA nanobots are synthetic nanometer-sized machines made of DNA and proteins. They’re autonomous because DNA itself is a self-assembling machine. Our natural DNA not only carries the code our biology is written in, it also knows when to execute. That’s part of the reason why, for example, your left and right feet tend to grow at roughly the same rate.”

Previous work in the field of DNA nanotechnology has demonstrated self-assembling machines capable of transferring DNA code, much like their natural counterparts. But the new tech out of Australia is unlike anything we’ve ever seen before.
Using the DNA origami receptor to demonstrate stable interactions with rapid exchange of both DNA and protein subunits, thus highlighting the applicability of the approach to arbitrary molecular cargo, an important distinction with canonical toehold exchange between single-stranded DNA. These particular nanobots can transfer more than just DNA information. Theoretically speaking, they could deliver any conceivable combination of proteins throughout a given biological system. To put that in simpler terms: the scientists should be able to eventually program swarms of these nanobots to hunt down bacteria, viruses, and cancer cells inside of our bodies. Each member of the swarm could carry a specific protein and, when they’ve found a bad cell, they could assemble their proteins into a formation designed to eliminate the threat.

Source: https://thenextweb.com/

Engineered Antibody Helps Block SARS-CoV-2 Transmission

Researchers at UC Davis Health have engineered a novel antibody, FuG1, that can directly interfere with the cell-to-cell transmission ability of SARS-CoV-2, the virus that causes COVID-19FuG1 targets the enzyme furin, which the  uses for its efficient chain of infections in human cells. The approach could be added to existing SARS-CoV-2 antibody cocktails for greater function against emerging variants.

We developed an approach that interferes with the transmission chain of SARS-CoV-2. The COVID-19 vaccines are a great lifesaver in reducing hospitalizations and severe illness. Yet, we are now learning that they may not be as effective in controlling the transmissibility of the virus,” said Jogender Tushir-Singh, senior author of the study.

Tushir-Singh is an associate professor in the Department of Medical Microbiology and Immunology and a member of the UC Davis Comprehensive Cancer Center therapeutics program. His research uses rational protein engineering to generate multi-targeting  as cancer therapeutics. When the pandemic hit, he began thinking of similar strategies that might work to limit the spread of the coronavirus.

Furin, found throughout the human body, is involved in various functions of cells. It is a type of enzyme, a protease, that can break down proteins into smaller components. It does this by cutting, or cleaving, the polybasic peptide bonds within the proteins. In cleaving these bonds, furin often acts as a switch, changing an inactive protein into an active one. For example, furin cleaves the inactive proparathyroid hormone into parathyroid hormone, which regulates calcium levels in the blood. It can also cleave and activate viruses that enter . Pathogens that utilize furin in their  include HIV, influenza, dengue fever and SARS-CoV-2.

When SARS-CoV-2 infects a human cell, it is in its active state, having already “cleaved” its , a key protein that binds to ACE2 receptors to gain entry. But when the virus is being synthesized within the host cell—when it is replicating—the  is in an inactive state. The virus needs to use the host cell’s furin to cut the spike protein into two parts, S1 and S2, which makes the spike active on the viral particles for efficient transmissibility upon release.

The virus exploits the host’s furin to transmit from one cell to another and another. This added activation step is what makes the virus highly transmissible,” said Tanmoy Mondal, the first author for the study and a post-doctoral researcher at UC Davis Health. But inhibiting furin to limit the SARS-CoV-2 chain of infection cycle is not a straightforward mechanism. “Furin is found throughout the  and is needed for the normal functioning of many biological processes. Stopping furin from doing its job causes high body toxicity. That is why the standard furin inhibitor drugs are not a clinically feasible option,” Tushir-Singh said.

Instead, he and his team engineered a conjugated antibody targeting the SARS-CoV-2 spike protein. The design is similar to therapeutic monoclonal (IgG) antibodies but includes an added featureFc-extended peptide—that specifically interferes with the host furin. The researchers named this approach FuG1.

A study evaluating the efficacy of the engineered antibody was published in Microbiology Spectrum.

Source: https://phys.org/

 

New copper surface eliminates bacteria in just two minutes

A new surface that kills bacteria more than 100 times faster and more effectively than standard copper could help combat the growing threat of antibiotic-resistant superbugs. The new copper product is the result of a collaborative research project with RMIT University and Australia’s national science agency, CSIRO, with findings just published in Biomaterials. Copper has long been used to fight different strains of bacteria, including the commonly found golden staph, because the ions released from the metal’s surface are toxic to bacterial cells. But this process is slow when standard copper is used, as RMIT University’s Distinguished Professor Ma Qian explained, and significant efforts are underway by researchers worldwide to speed it up.

The copper magnified 500,000 times under a scanning electron microscope shows the tiny nano-scale pores in the structure

A standard copper surface will kill about 97% of golden staph within four hours,” Qian said. “Incredibly, when we placed golden staph bacteria on our specially-designed copper surface, it destroyed more than 99.99% of the cells in just two minutes.” “So not only is it more effective, it’s 120 times faster.” Importantly, said Qian, these results were achieved without the assistance of any drug. “Our copper structure has shown itself to be remarkably potent for such a common material,” he said.

The team believes there could be a huge range of applications for the new material once further developed, including antimicrobial doorhandles and other touch surfaces in schools, hospitals, homes and public transport, as well as filters in antimicrobial respirators or air ventilation systems, and in face masks. The team is now looking to investigate the enhanced copper’s effectiveness against SARS-COV-2, the virus that causes COVID-19, including assessing 3D-printed samples. Other studies suggest copper may be highly effective against the virus, leading the US Environmental Protection Agency to officially approve copper surfaces for antiviral uses earlier this year.

Source: https://www.rmit.edu.au/news/

Two Studies Assess Pfizer’s Effectiveness Against Omicron

The Omicron variant substantially reduced antibody levels generated by the Pfizer-BioNTech COVID-19 vaccine, according to preliminary results from a South African study that’s still awaiting peer review. These are the first laboratory results to see how a COVID-19 vaccine holds up to Omicron. A team of researchers led by Africa Health Research Institute‘s Alex Sigal tested 14 blood samples from 12 people against a live sample of the Omicron variant. All 12 people were vaccinated, and six were previously infected.

Overall, the scientists found a roughly 40-fold reduction in the levels of neutralizing antibodies, the virus-fighting proteins that play a key role in our immune response, compared with the original version of the virus. Omicron did not evade vaccine protection completely, Sigal wrote on Twitter, meaning there’s still benefit to being vaccinated against this new variant. But the marked reduction in antibodies raises questions of how durable vaccine protection will be against Omicron – namely, whether booster shots will sufficiently ward off disease or if new vaccines may eventually be required. Sigal called it a “very large drop in neutralization of Omicron.”

A good booster probably would decrease your chance of infection, especially severe infection leading to more severe disease,” Sigal said in an online presentation of his results on Tuesday, according to Bloomberg. “People who haven’t had a booster should get one, and people who have been previously infected should be vaccinated.”

Shortly after Sigal announced his team’s results, another group of researchers at Sweden‘s Karolinska Institutet disclosed their own findings that suggested a substantial but less dramatic decline in antibody levels. The Karolinska team found a seven-fold reduction across 17 blood samples. They noted the impact of Omicron varied greatly between samples, and they used a version of Omicron that was artificially made in a lab instead of the live virus. A lead researcher for that group said the findings make Omicron “certainly worse than Delta, but, again, not as extreme as we expected.” The results are not finalized and have not been published in a medical journal. Sigal cautioned on Twitter that the findings “are likely to be adjusted as we do more experiments.”

Source: https://www.sciencealert.com/

World’s First COVID-19 DNA Vaccine

 India‘s drug regulator has granted emergency use approval for Zydus Cadila‘s COVID-19 vaccine, the world’s first DNA shot against the coronavirus, in adults and children aged 12 years and above. The approval gives a boost to India’s vaccination programme, which aims to inoculate all eligible adults by December, and will provide the first shot for those under 18, as the country still struggles to contain the virus spread in some states. The vaccine, ZyCoV-D, uses a section of genetic material from the virus that gives instructions as either DNA or RNA to make the specific protein that the immune system recognises and responds to. Unlike most COVID-19 vaccines, which need two doses or even a single dose, ZyCoV-D is administered in three doses.

The generic drugmaker, listed as Cadila Healthcare Ltd, aims to make 100 million to 120 million doses of ZyCoV-D annually and has already begun stockpiling the vaccineZydus Cadila‘s vaccine, developed in partnership with the Department of Biotechnology, is the second home-grown shot to get emergency authorization in India after Bharat Biotech‘s Covaxin. The drugmaker said in July its COVID-19 vaccine was effective against the new coronavirus mutants, especially the Delta variant, and that the shot is administered using a needle-free applicator as opposed to traditional syringes. The regulatory nod makes ZyCoV-D the sixth vaccine authorized for use in the country where only about 9.18% of the entire population has been fully vaccinated so far, according to Johns Hopkins data.

The firm had applied for the authorization of ZyCoV-D on July 1, based on an efficacy rate of 66.6% in a late-stage trial of over 28,000 volunteers nationwide.

https://www.reuters.com/