Viruses are uniquely designed to encapsulate genetic material within spherical protein shells, enabling them to replicate and invade host cells, often causing disease. Inspired by these complex structures, researchers have been exploring artificial proteins modeled after viruses. These “nanocages” mimic viral behavior, effectively delivering therapeutic genes to target cells. However, existing nanocages face significant challenges: their small size restricts the amount of genetic material they can carry, and their simple designs fall short of replicating the multifunctionality of natural viral proteins.

To address these limitations, the research team used AI-driven computational design. While most viruses display symmetrical structures, they also feature subtle asymmetries. Leveraging AI, the team recreated these nuanced characteristics and successfully designed nanocages in tetrahedral, octahedral, and icosahedral shapes for the first time.

The resulting nanostructures are composed of four types of artificial proteins, forming intricate architectures with six distinct protein-protein interfaces. Among these, the icosahedral structure, measuring up to 75 nanometers in diameter, stands out for its ability to hold three times more genetic material than conventional gene delivery vectors, such as adeno-associated viruses (AAV), marking a significant advancement in gene therapy.

Electron microscopy confirmed the AI-designed nanocages achieved precise symmetrical structures as intended. Functional experiments further demonstrated their ability to effectively deliver therapeutic payloads to target cells, paving the way for practical medical applications.

“Advancements in AI have opened the door to a new era where we can design and assemble artificial proteins to meet humanity’s needs,” said Professor Sangmin Lee. “We hope this research not only accelerates the development of gene therapies but also drives breakthroughs in next-generation vaccines and other biomedical innovations.”

Professor Lee previously worked as a postdoctoral researcher in Professor Baker’s laboratory at the University of Washington for nearly three years, from February 2021 to late 2023, before joining POSTECH in January 2024.

This study was supported by the Republic of Korea’s Ministry of Science and ICT under the Outstanding Young Scientist Program, the Nano and Material Technology Development Program, and the Global Frontier Research Program, with additional funding provided by the Howard Hughes Medical Institute (HHMI) in the United States.

Lithium-ion batteries are indispensable in applications such as electric vehicles and energy storage systems (ESS). The lithium-rich layered oxide (LLO) material offers up to 20% higher energy density than conventional nickel-based cathodes by reducing the nickel and cobalt content while increasing the lithium and manganese composition. As a more economical and sustainable alternative, LLO has garnered significant attention. However, challenges such as capacity fading and voltage decay during charge-discharge cycles have hindered its commercial viability.

While previous studies have identified structural changes in the cathode during cycling as the cause of these issues, the exact reasons behind the instability have remained largely unclear. Additionally, existing strategies aimed at enhancing the structural stability of LLO have failed to resolve the root cause, hindering commercialization.

The POSTECH team focused on the pivotal role of oxygen release in destabilizing the LLO structure during the charge-discharge process. They hypothesized that improving the chemical stability of the interface between the cathode and the electrolyte could prevent oxygen from being released. Building on this idea, they reinforced the cathode-electrolyte interface by improving the electrolyte composition, which resulted in a significant reduction in oxygen emissions.

The research team’s enhanced electrolyte maintained an impressive energy retention rate of 84.3% even after 700 charge-discharge cycles, a significant improvement over conventional electrolytes, which only achieved an average of 37.1% energy retention after 300 cycles.

The research also revealed that structural changes on the surface of the LLO material had a significant impact on the overall stability of the material. By addressing these changes, the team was able to dramatically improve the lifespan and performance of the cathode while also minimizing unwanted reactions like electrolyte decomposition inside the battery.

Professor Jihyun Hong commented, “Using synchrotron radiation, we were able to analyze the chemical and structural differences between the surface and interior of the cathode particles. This revealed that the stability of the cathode surface is crucial for the overall structural integrity of the material and its performance. We believe this research will provide new directions for developing next-generation cathode materials.”

This research was supported by the Ministry of Trade, Industry and Energy through the Korea Institute for Advancement of Technology, and the Ministry of Science and ICT through the National Research Foundation of Korea, with funding for 2024.

“With many current drugs to prevent migraine, it takes time to find the right dosage for the individual and it can take weeks or even months for it to be most effective,” said study author Richard B. Lipton, MD, of Albert Einstein College of Medicine in the Bronx, New York, and a Fellow of the American Academy of Neurology. “Some people give up and stop taking the drugs before they reach this point. Plus, many people experience side effects with current treatments. Developing a drug that works both effectively and quickly is critical.”

In the study, people taking the drug atogepant were less likely to have a migraine on the first day of taking the drug compared to those taking a placebo. They also had fewer migraines per week during each of the first four weeks of the study and fewer migraines during the study overall than those taking a placebo.

For this study, researchers looked at the data from three trials on the safety and effectiveness of atogepant over 12 weeks to focus on how rapidly improvements appeared. The ADVANCE trial, which enrolled people with episodic migraine, had 222 people taking the drug and 214 taking placebo. The ELEVATE trial, which enrolled people with episodic migraine who had previously not responded well to other oral preventive treatments, had 151 on the drug and 154 on placebo. The PROGRESS trial, which enrolled people with chronic migraine, had 256 on the drug and 246 on placebo.

People with episodic migraine experience up to 14 migraine days per month. People with chronic migraine experience at least 15 days with headache per month, with at least eight days being characteristic of migraine.

On the first day of the study, 12% of those taking the drug in the first trial, the ADVANCE trial had a migraine, compared to 25% of those taking placebo. In the second trial, the ELEVATE trial, the numbers were 15% and 26%. For the third trial, the PROGRESS trial, the numbers were 51% and 61%.

When researchers adjusted for other factors that could affect the rate of migraine, they found that people taking the drug were 61% less likely to have a migraine in the first trial, 47% less likely in the second trial, and 37% less likely in the third trial.

For the first two trials, the people taking atogepant had an average of one fewer day with migraine per week, compared to an average of less than one-half day fewer per week for those taking the placebo. For the third trial, average migraine days per week declined by about 1.5 days for those taking the drug compared to about one day for those taking the placebo.

The people taking atogepant also showed improvement on assessments of how much migraine impaired their activities and their overall quality of life compared to people taking the placebo.

“Migraine is the second-leading cause of disability in the overall population and the leading cause of disability in young women, with people reporting negative effects on their relationships, parenting, career and finances,” Lipton said. “Having a treatment that can act quickly and effectively addresses a key need.”

A limitation of the study is that it involved mostly female and white participants, so the results may not apply to the overall population.

The study was supported by AbbVie, the maker of atogepant.

The application in live mice shows the improved efficiency of the tool, called SPLICER, over the current standard in gene editing technology, as well as the potential for application in other diseases, the researchers said. Led by Pablo Perez-Pinera, a professor of bioengineering at the U. of I., the researchers published their findings in the journal Nature Communications.

SPLICER uses a gene editing approach called exon skipping, which is of particular interest for health conditions caused by mutations that produce misfolded or toxic proteins, such as Duchenne’s muscular dystrophy or Huntington’s disease.

“DNA contains the instructions to build everything that is responsible for how cells function. So it’s like a book of recipes that contains very detailed instructions for cooking,” Perez-Pinera said. “But there are large regions of DNA that don’t code for anything. It’s like, you start the recipe for a turkey dinner, and then you hit a note that says, ‘continued on page 10.’ After page 10, it’s ‘continued on page 25.’ The pages between are gibberish.

“But say on one of the recipe pages — in genetics, an exon — there is a typo that makes the turkey inedible, or even poisonous. If we cannot correct the typo directly, we could amend the note before it to send you to the next page, skipping over the page with the error, so that at the end you could make an edible turkey. Though you might lose out on the gravy that was on the skipped page, you’d still have dinner. In the same way, if we can skip the piece of the gene with the toxic mutation, the resulting protein could still have enough function to perform its critical roles.”

SPLICER builds upon the popular CRISPR-Cas9 gene editing platform — with key changes. CRISPR-Cas9 systems require a specific DNA sequence to latch on, limiting which genes could be edited. SPLICER uses newer Cas9 enzymes that do not need that sequence, opening up the door to new targets like the Alzheimer’s-related gene that the Illinois group focused on.

“Another problem we address in our work is precision in what gets skipped,” said graduate student Angelo Miskalis, a co-first author of the paper. “With current exon-skipping techniques, sometimes not all of the exon gets skipped, so there’s still part of the sequence we don’t want expressed. In the cookbook analogy, it’s like trying to skip a page, but the new page starts in the middle of a sentence, and now the recipe doesn’t make sense. We wanted to prevent that.”

There are two key sequence areas surrounding an exon that tell the cellular machinery which parts of a gene to use for making proteins: one at the beginning and one at the end. While most exon-skipping tools target only one sequence, SPLICER edits both the starting and ending sequences. As a result, the targeted exons are skipped over more efficiently, Miskalis said.

The Illinois group chose to target an Alzheimer’s gene for the first demonstration of SPLICER’s therapeutic abilities because while the target gene has been well-studied, efficient exon skipping has remained elusive in living organisms. The researchers targeted a specific exon coding for an amino acid sequence within a protein that gets cleaved to form amyloid-beta, which accumulates to form plaques on neurons in the brain as the disease progresses.

In cultured neurons, SPLICER reduced the formation of amyloid-beta efficiently. When analyzing the DNA and RNA output of mouse brains, the researchers found that the targeted exon was decreased by 25% in the SPLICER-treated mice, with no evidence of off-target effects.

“When we originally tried to target this exon with older techniques, it didn’t work,” said graduate student Shraddha Shirguppe, also a co-first author of the study. “Combining the newer base editors with dual splice editing skipped the exon at a much better rate than we were previously able to with any of the available methods. We were able to show that not only could it skip the whole exon better, it reduced the protein that produces the plaque in these cells.”

“Exon skipping only works if the resulting protein is still functional, so it can’t treat every disease with a genetic basis. That’s the overall limitation of the approach,” Perez-Pinera said. “But for diseases like Alzheimer’s, Parkinson’s, Huntington’s or Duchenne’s muscular dystrophy, this approach holds a lot of potential. The immediate next step is to look at the safety of removing the targeted exons in these diseases, and make sure we aren’t creating a new protein that is toxic or missing a key function. We would also need to do longer term animal studies and see if the disease progresses over time.”

At Illinois, Perez-Pinera also is affiliated with the department of Molecular and Integrative Physiology, the Carle Illinois College of Medicine, the Cancer Center at Illinois and the Carl R. Woese Institute for Genomic Biology. U. of I. Bioengineering professors Sergei Maslov and Thomas Gaj were coauthors of the paper. The National Institutes of Health, the Muscular Dystrophy Association, the American Heart Association, the Parkinson’s Disease Foundation and the Simons Foundation supported this work.

This work was supported by the National Institutes of Health grants 1U01NS122102, 1R01NS123556, 1R01GM141296, 1R01GM127497, T32EB019944 and 1R01GM131272.

The research involved a bismuth complex synthesized in the group of Josep Cornella (MPI KOFO). This molecule has unique magnetic properties that a team led by Frank Neese (MPI KOFO) recently predicted in theoretical studies. So far, however, all attempts to measure the magnetic properties of the bismuth complex and thus experimentally confirm the theoretical predictions have failed.

This important step has now been achieved by using THz electron paramagnetic resonance spectroscopy (THz-EPR) at the synchrotron radiation source BESSY II, which is operated by the HZB in Berlin.

“The results show in a fascinating way that our method can be used to determine extremely high values of the magnetic anisotropy with high accuracy. Through our cooperation with scientists from fundamental research, we are thereby making a great step forward in the understanding of this class of materials,” says Tarek Al Said (HZB), first author of the study, which was recently published in the Journal of the American Chemical Society.

People with Parkinson’s disease report that tremors worsen during stressful situations. ‘Tremors act as a sort of barometer for stress; you see this in all people with Parkinson’s’, says neurologist Rick Helmich from Radboud university medical center. The commonly used drug levodopa usually helps with tremors, but it tends to be less effective during stress, when tremors are often at their worst. Helmich and his team wanted to investigate whether a medication targeting the stress system could help and how this effect of stress on tremors works in the brain.

Mathematical calculations

The medication in question, propranolol, is a beta-blocker that inhibits the action of stress hormones. It was developed for high blood pressure and heart arrhythmias, has been around for a long time, and is already used as a standard treatment for essential tremor — a condition in which people experience tremors without other neurological symptoms. There were already indications that propranolol might reduce tremors in Parkinson’s, but until now, no thorough research has explored its potential effects.

Helmich and his team studied 27 people with Parkinson’s who experienced tremors. They were given propranolol on one day and a placebo on another day. A device on their hands measured the intensity of their tremors, while an MRI scan mapped brain activity. This was done both at rest and during a task involving stressful mathematical calculations. The stress response was measured by pupil size and heart rate, both of which increased during the calculations. As expected, without medication, tremors worsened during stress.

Amplifier

The study showed that propranolol reduced tremors both at rest and during stress. The MRI scans revealed how this works: after taking the medication, the brain circuit responsible for tremors showed less activity. Helmich explains: ‘We know that abnormalities in systems like the dopamine system cause tremors. Based on our study, we now think that the stress hormone noradrenaline acts as an amplifier, which increases tremor intensity in the brain’s movement area. Propranolol inhibits this amplifying effect and thus reduces symptoms.’

It surprised the researchers that propranolol also worked to reduce tremors at rest. ‘Apparently, our stress system is occasionally active, even at rest’, says researcher Anouk van der Heide. ‘This changes how alert someone is and leads to spontaneous fluctuations in tremors. We previously thought that the stress hormone system was only active under stress, but apparently, that’s too simplistic. It also plays a role at rest.’

Mindfulness

Helmich already prescribes propranolol for some Parkinson’s patients. ‘The most effective medication for Parkinson’s is levodopa. It not only helps with tremors but also with other symptoms, so that’s what we start with’, Helmich explains. ‘However, in about forty percent of patients, it is not effective against tremors. In that case, we first increase the dose, but if that doesn’t work, propranolol is an option. However, we must be cautious about side effects, such as low blood pressure.’

In addition to medication studies, Helmich’s team is also exploring lifestyle changes that could help with Parkinson’s. ‘It doesn’t take much to trigger a stress response, causing people to tremble more. Even something as simple as wondering: did I lock the front door? can set it off. We are currently investigating whether mindfulness can positively influence the stress system.’

Deep-sea temperature is stable, with only minor changes occurring even over long-time scales. Despite this stability, deep-sea organisms are highly adapted to such stable environments, making them particularly sensitive to even slight temperature fluctuations. Unlike surface water, the deep sea lacks primary production due to the absence of sunlight, which prevents phytoplankton growth and photosynthesis. Instead, deep-sea organisms rely on food that descends from the ocean surface, known as particulate organic material or marine snow. This includes dead plankton, a primary food source of organisms living on the deep ocean floor.

A new study conducted by the research team, utilising empirical data from deep-sea fossils extracted from sediment cores spanning 500,000 years, clearly demonstrated that temperature and food input have significantly modified deep-sea communities over long time scales, each affecting different species.

Professor Yasuhara stated, ‘It’s important not only to advance fundamental science by understanding how ecosystems on our planet operate but also to address the growing challenges posed by human-induced climatic change.’

As global concern over ongoing human-induced climatic warming and its future escalation intensifies, scientists and engineers are working hard to develop mitigation technologies to combat climatic change. These geoengineering technologies, collectively referred to as ocean-based climate intervention (OBCI), include approaches such as marine carbon dioxide removal (mCDR), which aim to reduce future warming by putting and storing carbon or carbon dioxide in deep-sea sediment, where they remain stable due to the low-temperature and high-pressure environments.

One prominent example of mCDR is iron fertilisation, a process in which iron is added to the ocean surface to enhance primary production, resulting in increased sinking of organic carbon to the deep-sea floor. While mCDR and OBCI are technologically advanced and nearly ready for implementation, they have yet to be deployed on large scales. One major concern is how these technologies will affect deep-sea ecosystems.

Yasuhara continues, ‘Deep sea covers over 40% of our planet’s surface, and its ecosystem is known to be highly vulnerable. The deep sea also harbours countless species that are still undiscovered. I would say the vast majority of species remain unknown to us. Our study, using a fossil record from a deep-sea sediment core for the past 500,000 years, shows that both temperature and food input, driven by changes in natural iron fertilisation through dust input and the resulting surface production enhancement, have altered deep-sea ecosystems in different ways substantially. This means we must be cautious when making decisions about this important and delicate ecosystem. Careful ecosystem impact assessments are needed to evaluate, on a case-by-case basis, whether human-induced warming or mCDR involving surface productivity changes is more harmful. Only then can we make a cautious and sensible decision about whether to proceed with mCDR.’

Professor Yasuhara also remarked that the Southern Ocean can be seen as a ‘canary in a coal mine’ because it’s a key sensitive region in the global ocean circulation and climatic system. ‘Our study highlights the sensitivity of its deep-sea ecosystem. Increased deep-sea biological monitoring efforts in this region are needed, as it could provide early warning signals of climatic changes. Our study also showed that the present-day style of the deep-sea ecosystem in the Southern Ocean was established 430,000 years ago. I hope such a long-standing ecosystem won’t be completely altered in the near future, especially since we don’t know how much this human-induced warming will escalate and fundamentally change our global climatic system in future.’