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Biomedical engineers at Duke University have developed a self-assembling nanomaterial that can help limit damage caused by inflammatory diseases by activating key cells in the immune system. In mouse models of psoriasis, the nanofiber-based drug has been shown to mitigate damaging inflammation as effectively as a gold-standard therapy. One of the hallmarks of inflammatory diseases, like rheumatoid arthritis, Crohn’s disease and psoriasis, is the overproduction of signaling proteins, called cytokines, that cause inflammation. One of the most significant inflammatory cytokines is a protein called TNF. Currently, the best treatment for these diseases involves the use of manufactured antibodies, called monoclonal antibodies, which are designed to target and destroy TNF and reduce inflammation.
Although monoclonal antibodies have enabled better treatment of inflammatory diseases, the therapy is not without its drawbacks, including a high cost and the need for patients to regularly inject themselves. Most significantly, the drugs also have uneven efficacy, as they may sometimes not work at all or eventually stop working as the body learns to make antibodies that can destroy the manufactured drug. To circumvent these issues, researchers have been exploring how immunotherapies can help teach the immune system how to generate its own therapeutic antibodies that can specifically limit inflammation.
The graphic shows the peptide nanofiber bearing complement protein C3dg (blue) and key components of the TNF protein, which include B-cell epitopes (green), and T-cell epitopes (purple)
“We’re essentially looking for ways to use nanomaterials to induce the body’s immune system to become an anti-inflammatory antibody factory,” said Joel Collier, a professor of biomedical engineering at Duke University. “If these therapies are successful, patients need fewer doses of the therapy, which would ideally improve patient compliance and tolerance. It would be a whole new way of treating inflammatory disease.”
In their new paper, which appeared online in the Proceedings of the National Academy of Sciences (PNAS), Collier and Kelly Hainline, a graduate student in the Collier lab, describe how novel nanomaterials could assemble into long nanofibers that include a specialized protein, called C3dg. These fibers then were able to activate immune system B-cells to generate antibodies. “C3dg is a protein that you’d normally find in your body,” said Hainline. “The protein helps the innate immune system and the adaptive immune system communicate, so it can activate specific white blood cells and antibodies to clear out damaged cells and destroy antigens.”
Due to the protein’s ability to interface between different cells in the immune system and activate the creation of antibodies without causing inflammation, researchers have been exploring how C3dg could be used as a vaccine adjuvant, which is a protein that can help boost the immune response to a desired target or pathogen.
If the CO2 content of the atmosphere is not to increase any further, carbon dioxide must be converted into something else. However, as CO2 is a very stable molecule, this can only be done with the help of special catalysts. The main problem with such catalysts has so far been their lack of stability: after a certain time, many materials lose their catalytic properties.
At TU Wien (Austria), research is being conducted on a special class of minerals – the perovskites, which have so far been used for solar cells, as anode materials or electronic components rather than for their catalytic properties. Now scientists at TU Wien have succeeded in producing a special perovskite that is excellently suited as a catalyst for converting CO2 into other useful substances, such as synthetic fuels. The new perovskite catalyst is very stable and also relatively cheap, so it would be suitable for industrial use.
“We are interested in the so-called reverse water-gas shift reaction,” says Prof. Christoph Rameshan from the Institute of Materials Chemistry at TU Wien. “In this process, carbon dioxide and hydrogen are converted into water and carbon monoxide. You can then process the carbon monoxide further, for example into methanol, other chemical base materials or even into fuel.”
This reaction is not new, but it has not really been implemented on an industrial scale for CO2 utilisation. It takes place at high temperatures, which contributes to the fact that catalysts quickly break down. This is a particular problem when it comes to expensive materials, such as those containing rare metals.
Christoph Rameshan and his team investigated how to tailor a material from the class of perovskites specifically for this reaction, and he was successful: “We tried out a few things and finally came up with a perovskite made of cobalt, iron, calcium and neodymium that has excellent properties,” says Rameshan.
Because of its crystal structure, the perovskite allows certain atoms to migrate through it. For example, during catalysis, cobalt atoms from the inside of the material travel towards the surface and form tiny nanoparticles there, which are then particularly chemically active. At the same time, so-called oxygen vacancies form – positions in the crystal where an oxygen atom should actually sit. It is precisely at these vacant positions that CO2 molecules can dock particularly well, in order to then be dissociated into oxygen and carbon monoxide.
“We were able to show that our perovskite is significantly more stable than other catalysts,” says Christoph Rameshan. “It also has the advantage that it can be regenerated: If its catalytic activity does wane after a certain time, you can simply restore it to its original state with the help of oxygen and continue to use it.”
Initial assessments show that the catalyst is also economically promising. “It is more expensive than other catalysts, but only by about a factor of three, and it is much more durable,” says Rameshan. “We would now like to try to replace the neodymium with something else, which could reduce the cost even further.“Theoretically, you could use such technologies to get CO2 out of the atmosphere – but to do that you would first have to concentrate the carbon dioxide, and that requires a considerable amount of energy. It is therefore more efficient to first convert CO2 where it is produced in large quantities, such as in industrial plants. “You could simply add an additional reactor to existing plants that currently emit a lot of CO2, in which the CO2 is first converted into CO and then processed further,” says Christoph Rameshan. Instead of harming the climate, such an industrial plant would then generate additional benefits.
Michael Wallace has performed hundreds of colonoscopies in his 20 years as a gastroenterologist. He thinks he’s pretty good at recognizing the growths, or polyps, that can spring up along the ridges of the colon and potentially turn into cancer. But he isn’t always perfect. Sometimes the polyps are flat and hard to see. Other times, doctors just miss them. “We’re all humans,” says Wallace, who works at the Mayo Clinic. After a morning of back-to-back procedures that require attention to minute details, he says, “we get tired.”
Colonoscopies, if unpleasant, are highly effective at sussing out pre-cancerous polyps and preventing colon cancer. But the effectiveness of the procedure rests heavily on the abilities of the physician performing it. Now, the Food and Drug Administration has approved a new tool that promises to help doctors recognize precancerous growths during a colonoscopy: an artificial intelligence system made by Medtronic. Doctors say that alongside other measures, the tool could help improve diagnoses.
“We really have the opportunity to completely wipe out colon cancer in anybody who gets screened,” says Wallace, who consulted with Medtronic on the project.
The Medtronic system, called GI Genius, has seen the inside of more colons than most doctors. Medtronic and partner Cosmo Pharmaceuticals trained the algorithm to recognize polyps by reviewing more than 13 million videos of colonoscopies conducted in Europe and the US that Cosmo had collected while running drug trials. To “teach” the AI to distinguish potentially dangerous growths, the images were labeled by gastroenterologists as either normal or unhealthy tissue. Then the AI was tested on progressively harder-to-recognize polyps, starting with colonoscopies that were performed under perfect conditions and moving to more difficult challenges, like distinguishing a polyp that was very small, only in range of the camera briefly, or hidden in a dark spot. The system, which can be added to the scopes that doctors already use to perform a colonoscopy, follows along as the doctor probes the colon, highlighting potential polyps with a green box. GI Genius was approved in Europe in October 2019 and is the first AI cleared by the FDA for helping detect colorectal polyps. “It found things that even I missed,” says Wallace, who co-authored the first validation study of GI Genius. “It’s an impressive system.”
Osteoarthritis (OA), the most common form of arthritis, affects over 32 million people in the U.S. each year. Characterized by a progressive degeneration of cartilage resulting in pain, stiffness, and swelling in the joints, and most frequently occurring in the hands, hips, and knees, OA has no pharmacological, biological, or surgical treatment to prevent progression of the condition. The authors of this case report focus specifically on potential treatment options for OA of the knee.
With the emergence of stem cell-based therapies for a multitude of health conditions, stem cells, and specifically mesenchymal stem cells (MSCs), have demonstrated immunosuppressive activities that could prove beneficial in supporting the regeneration of cartilage tissue in and around joints in the body.
Research has demonstrated that MSCs are effective in differentiating into essential connective tissues like fat, cartilage, and bone; MSCs have also demonstrated immunomodulatory and anti-inflammatory effects, the ability to self-renew, and plasticity, making MSCs a potentially powerful treatment of OA in the knee (and other parts of the body).
This specific case study details cartilage regeneration in the knee of a 47-year-old woman diagnosed with OA when treated with bone marrow-derived MSC cells. For the course of this treatment, autologous MSCs were collected from bone marrow harvested from the iliac crest. After processing and preparing the MSCs, the sample was confirmed to be free of microbial contamination and was prepared and transplanted into the patient’s knee joint.
Periodic follow-ups with the patient revealed no local or systemic adverse events associated with the MSC transplant procedure. The authors of this case report found that the patient’s functional status of her knee, the number of stairs she could climb, reported pain on a visual analog scale, and walking distance all improved in the two months following the MSC transplant procedure.
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 design” platform 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.
A small, light-activated molecule recently tested in mice represents a new approach to eliminating clumps of amyloid protein found in the brains of Alzheimer’s disease patients. If perfected in humans, the technique could be used as an alternative approach to immunotherapy and used to treat other diseases caused by similar amyloids. Researchers injected the molecule directly into the brains of live mice with Alzheimer’s disease and then used a specialized probe to shine light into their brains for 30 minutes each day for one week. Chemical analysis of the mouse brain tissue showed that the treatment significantly reduced amyloid protein. Results from additional experiments using human brain samples donated by Alzheimer’s disease patients supported the possibility of future use in humans.
“The importance of our study is developing this technique to target the amyloid protein to enhance clearance of it by the immune system,” said Yukiko Hori, a lecturer at the University of Tokyo and co-first author of the research recently published in Brain. The small molecule that the research team developed is known as a photo-oxygenation catalyst. It appears to treat Alzheimer’s disease via a two-step process.
First, the catalyst destabilizes the amyloid plaques. Oxygenation, or adding oxygen atoms, can make a molecule unstable by changing the chemical bonds holding it together. Laundry detergents or other cleaners known as “oxygen bleach” use a similar chemical principle. The catalyst is designed to target the folded structure of amyloid and likely works by cross-linking specific portions called histidine residues. The catalyst is inert until it is activated with near-infrared light, so in the future, researchers imagine that the catalyst could be delivered throughout the body by injection into the bloodstream and targeted to specific areas using light.
Second, the destabilized amyloid is then removed by microglia, immune cells of the brain that clear away damaged cells and debris outside healthy cells. Using mouse cells growing in a dish, researchers observed microglia engulfing oxygenated amyloid and then breaking it down in acidic compartments inside the cells. “Our catalyst binds to the amyloid-specific structure, not to a unique genetic or amino acid sequence, so this same catalyst can be applied to other amyloid depositions,” said Professor Taisuke Tomita, who led the project at the University of Tokyo.
The American Society of Clinical Oncology estimates that each year in the U.S., 4,000 people are diagnosed with diseases caused by amyloid outside of the brain, collectively known as amyloidosis. The photo-oxygenation catalyst should be capable of removing amyloid protein, regardless of when or where it formed in the body. Although some existing Alzheimer’s disease treatments can slow the formation of new amyloid plaques, eliminating existing plaques is especially important in Alzheimer’s disease because amyloid begins aggregating years before symptoms appear.
In a study published in the Journal of Materials Chemistry A, the researchers led by Professor Hongxia Wang in collaboration with Associate Professor Prashant Sonar of the Queensland University of technology (QUT) in Australia showed the carbon nanodots could be used to improve the performance of perovskites solar cells, a relatively new photovoltaic technology, are seen as the best PV candidate to deliver low-cost, highly efficient solar electricity in coming years. They have proven to be as effective in power conversion efficiency as the current commercially available monocrystalline silicon solar cells, but the hurdles for researchers in this area is to make the technology cheaper and more stable. Unlike silicon cells, they are created with a compound that is easily manufactured, and as they are flexible they could be used in scenarios such as solar-powered clothing, backpacks that charge your devices on the go and even tents that could serve as standalone power sources.
This is the second major piece of research to come as a result of a human hair derived carbon dots as multifunctional material. Last year, Associate Professor Prashant Sonar led a research team, including Centre for Materials Science research fellow Amandeep Singh Pannu, that turned hair scraps into carbon nanodots by breaking down the hairs and then burning them at 240 degrees celsius. In that study, the researchers showed the carbon dots could be turned into flexible displays that could be used in future smart devices.
In this new study, Professor Wang’s research team, including Dr Ngoc Duy Pham, and Mr Pannu, working with Professor Prashant Sonar’s group, used the carbon nanodots on perovskite solar cells out of curiosity. Professor Wang’s team had previously found that nanostructured carbon materials could be used to improve a cell’s performance. After adding a solution of carbon dots into the process of making the perovskites, Professor Wang’s team found the carbon dots forming a wave-like perovskite layer where the perovskite crystals are surrounded by the carbon dots.
“It creates a kind of protective layer, a kind of armour,” Professor Wang said. “It protects the perovskite material from moisture or other environmental factors, which can cause damage to the materials.”
The study found that perovskite solar cells covered with the carbon dots had a higher power conversion efficiency and a greater stability than perovskite cells without the carbon dots.