Messenger RNAs with multiple “tails” could lead to more effective therapeutics

Graphic showing scientists adding "tails" to mRNA molecules
Illustration Credit: Catherine Boush, Broad Communications

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers from the Broad Institute and MIT engineered a novel mRNA structure containing multiple poly(A) "tails" that significantly enhances molecular stability and translation efficiency.
• Methodology: The team chemically synthesized branched mRNA topologies and assessed their performance in human cells and murine models, including integration with CRISPR-Cas9 systems for gene editing.
• Key Data: The multi-tailed mRNA increased protein activity in cells by 5 to 20 times and sustained protein production in mice for 14 days, lasting two to three times longer than unmodified molecules.
• Significance: This innovation addresses the limitation of rapid mRNA degradation, allowing for sustained therapeutic effects at lower doses which minimizes the risk of toxic side effects.
• Future Application: Potential uses include long-lasting treatments for diseases requiring gene editing or protein replacement, such as therapeutic interventions for high cholesterol.
• Branch of Science: Biotechnology and Bioengineering
• Additional Detail: The study demonstrates that cellular translation machinery readily accepts synthetic, non-natural mRNA shapes, validating the potential for extensive chemical topological engineering.

What Is: mRNA

The Genetic Messenger
Messenger RNA (mRNA) serves as the vital intermediary in the "central dogma" of molecular biology, bridging the gap between stable genomic DNA and the production of functional proteins. Acting as a transient transcript, mRNA carries specific genetic instructions from the cell nucleus to the ribosome, where the code is translated into precise amino acid sequences. By providing a temporary, programmable blueprint for cellular machinery, mRNA enables the dynamic regulation of life’s essential processes and stands as a cornerstone of modern biotechnological innovation.

Scientific Frontline: Extended "At a Glance" Summary

The Core Concept: Messenger RNA (mRNA) acts as a transient biological intermediary that conveys specific genetic instructions from cellular DNA to ribosomes, serving as a programmable blueprint for the synthesis of functional proteins.

Key Distinction/Mechanism: Unlike traditional pharmaceuticals that deliver the "hardware" (such as small molecule inhibitors or recombinant proteins), mRNA therapeutics deliver the "software" (genetic code), instructing the patient's own cells to manufacture the therapeutic agent. This process is inherently transient; the molecule degrades naturally without integrating into the host genome, eliminating the risk of insertional mutagenesis associated with DNA-based gene therapies.

mRNA vaccines follow unconventional immune path to destroy tumors

WashU Medicine researchers have described how mRNA cancer vaccines engage the immune system, through an unconventional pathway involving two subsets of immune cells called dendritic cells.
Image Credit: Sara Moser/WashU Medicine

Scientific Frontline: Extended "At a Glance" Summary: mRNA Cancer Vaccine Immune Pathways

The Core Concept: Washington University researchers have discovered that mRNA cancer vaccines activate anti-tumor immune responses through an unconventional pathway utilizing two distinct subsets of dendritic cells. This challenges the previous assumption that only one specific immune cell subtype was required for these vaccines to effectively target and destroy tumors.

Key Distinction/Mechanism: Traditionally, cDC1 (classical type 1 dendritic cells) were thought to be the primary activators of T cells against viruses and tumors. However, this research demonstrates that a related subtype, cDC2, also independently stimulates strong T-cell responses. The cDC2 cells accomplish this through a "cross-dressing" mechanism, where they outsource the translation and processing of mRNA instructions to other cells, subsequently acquiring the resulting protein fragments on their own cellular membranes to engage T cells.

Major Frameworks/Components:

• Messenger RNA Biomolecules: Delivered instructions that prompt immune cells to synthesize specific tumor protein fragments.
• Dendritic Cell Subsets (cDC1 and cDC2): Antigen-presenting cells responsible for priming the immune system. Both subsets are now proven necessary for an optimal anti-tumor response.
• T-Cell Activation: The generation of specialized "seek and destroy" immune cells, which exhibit distinct molecular "fingerprints" depending on whether they were activated by cDC1 or cDC2 cells.
• Cellular "Cross-Dressing": An unconventional process where cDC2 cells acquire intact antigen-membrane complexes from adjacent cells rather than translating the mRNA themselves.

Efficient mRNA delivery by branched lipids

A cross-section of an LNP-RNA. The mRNA (red) is encapsulated by lipids (blue spheres with tails.
 Image Credit: Yusuke Sato

Scientific Frontline: "At a Glance" Summary

• Main Discovery: A novel branched ionizable lipid, CL4F 8-6, significantly improves the storage stability and intracellular delivery efficiency of mRNA encapsulated in lipid nanoparticles (LNPs).
• Methodology: Researchers synthesized a systematic library of 32 branched ionizable lipids defined by symmetry and carbon number, then screened them to identify correlations between lipid structure, microviscosity, and in vivo performance.
• Key Data: The optimized lipid formulation achieved a 77% suppression of a target gene in mice following a single dose.
• Significance: This research establishes a positive correlation between lipid symmetry/microviscosity and LNP stability, overcoming previous barriers in systematic lipid analysis and enhancing gene editing potential.
• Future Application: Development of more stable and effective mRNA vaccines and gene-editing therapies with targeted organ selectivity.
• Branch of Science: Pharmaceutical Sciences and Nanotechnology
• Additional Detail: The study identified that the length of the branched lipid chains directly influences which organs, specifically the liver or spleen, express the delivered proteins.

How faulty mRNA is destroyed

Image Credit: Scientific Frontline

Scientific Frontline: Extended "At a Glance" Summary: Nonsense-Mediated mRNA Decay (NMD)

The Core Concept: Nonsense-mediated mRNA decay (NMD) is an essential cellular quality-control process that inspects messenger RNA (mRNA) for errors and selectively degrades faulty or incomplete transcripts to prevent the synthesis of defective proteins.

Key Distinction/Mechanism: Unlike permanently active enzymes that could cause collateral damage to healthy mRNA, the NMD system relies on a precise safety mechanism. The proteins SMG5 and SMG6 have little to no cutting activity individually; however, when they interact, they form a highly active endonuclease—a molecular "pair of scissors"—that targets and cleaves flawed RNA with strict spatial and temporal precision.

Origin/History: While the individual proteins involved in this mechanism have been recognized for approximately 20 years, the exact nature of their interaction was recently solved by a collaborative research team from the University of Cologne and the Max Planck Institute of Biochemistry.

Major Frameworks/Components: 

• Messenger RNA (mRNA): The genetic blueprint copied from DNA, which dictates protein production.
• Nonsense-Mediated mRNA Decay (NMD): The overarching surveillance pathway that identifies transcript errors.
• SMG5 and SMG6 Proteins: The specific molecular components that interact to execute the destruction of faulty mRNA.
• Endonuclease Activity: The enzymatic cutting process resulting from the composite formation of the SMG5-SMG6 PIN domain.

Optimization of mRNA containing nanoparticles

Dr. Aurel Radulescu at the KWS-2 instrument of the Juelich Center for Neutron Science (JCNS) in the research neutron source Heinz Maier-Leibnitz (FRM II) of the Technical University of Munich
Image: Bernhard Ludewig / TUM / FRM II

The research neutron source Hein Maier-Leibnitz (FRM II) at the Technical University of Munich (TUM) is playing an important role in the investigation of mRNA nanoparticles similar to the ones used in the Covid-19 vaccines from vendors BioNTech and Pfizer. Researchers at the Heinz Maier-Leibnitz Zentrum (MLZ) used the high neutron flux available in Garching to characterize various formulations for the mRNA vaccine and thus to lay the groundwork for improving the vaccine's efficacy.

The idea of using messenger RNA (mRNA) as an active ingredient is a brilliant one: The molecule contains the specific blueprint for proteins which are then synthesize by the cell. This makes it generally possible to provide a very wide spectrum of different therapeutically effective proteins.

In the case of the Covid-19 vaccine, these are the proteins of the characteristic spikes on the surface of the Corona virus which are used for vaccination. The proteins are presented on the surface of immune cells; then the human immune system triggers defenses against these foreign proteins and thus against the Corona virus. The mRNA itself is completely broken down after only a few hours, a fact which is advantageous to the safety of these vaccines.

The mRNA has to be packaged appropriately in order to keep it from being broken down on the way to the cell by the ubiquitous enzymes of the human body. This is done using nanoparticles which can consist of a mixture of lipids or polymers.

A rare Tibetan worm may hold key to long-acting COVID vaccines

 

Caterpillars with emerging Ophiocordyceps sinensis
Credit: William Rafti Institute

A molecule isolated from the world’s most valuable parasite, the caterpillar fungus (Ophiocordyceps sinensis), may provide clues to better and more stable mRNA vaccines, according to research being done in Australia.

The molecule was first isolated from cordyceps fungi in the 1950s. These fungi infect ghost moth larvae, to make 'summer grass' prized in Tibetan and Chinese medicines for its benefits as a tonic and as a treatment for sexual dysfunction.

Associate Professor Traude Beilharz, from the Biomedicine Discovery Institute at Monash University in Melbourne, and her team have been studying the cordycepin molecule because of its ability to trick cells into increasing nucleotides and making mRNA with longer 3'UTRs. According to Associate Professor Beilharz, understanding how 3' UTRs work is really important to improving the stability and function of vaccines. Their research was recently published in the eLife journal.

The lab is now using what they have learned about 3'UTRs from that study to create a screening

Associate Professor Traude Beilharz

platform to identify optimal 3'UTRs for new mRNA vaccines. These 3’UTRs are crucial in stimulating immunity and may reduce the need for booster shots to maintain this immunity. Rachael Turner, first author of the study, has nearly completed her PhD thesis. Next she will apply her expertise in 3’ UTR function toward improving future mRNA vaccines.

The caterpillar fungus, Ophiocordyceps sinensis, is the world’s most valuable parasite. It’s a relative of the tropical fungus that turns ants into zombies, but unlike its infamous cousin, it is found only on the Tibetan plateau, where it infects the larvae of ghost moths. It has long been part of traditional Chinese medicine, and demand for it has risen so sharply in recent decades that in Beijing it is now worth three times its weight in gold. In Bhutan, one of the countries where the fungus is harvested, it accounts for a significant slice of the gross domestic product.

The development of mRNA vaccines, largely due to COVID-19, has been rapid. In addition, the development of mRNA vaccines against cancer has also developed at pace. According to Associate Professor Beilharz, “mRNA vaccines are a promising technology as the production process is simple, safety profiles are better than those of DNA vaccines, and mRNA-encoded antigens are readily expressed in cells, which stimulate immunity against the virus.”

However, mRNA vaccines also possess some inherent limitations. While side effects such as allergy, renal failure, heart failure, and infarction remain a risk, the vaccine mRNA may also be degraded quickly after administration, leading to the need for boosters.

The best types of mRNA vaccines are those that only encode the target antigen (in the case of COVID vaccines, the spike protein) and contain 5' and 3' untranslated regions (UTRs), which provide comprehensive stimulation of the adaptive and innate immunity. “Studying the cordyceps fungi molecule and how it can be used to understand the function of 3’UTRs is a key step in making better vaccines against infectious diseases like COVID-19 and also cancers,” Associate Professor Beilharz said.

Monash is home to Australia's largest network of RNA and mRNA researchers. Keep up to date with our work on life-saving vaccines and therapeutic treatments on the Monash RNA webpage.

Source/Credit: Monash University

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A key mechanism that controls human heart development discovered

A human cardiac organoid (Cardioid), one of the models the researchers used to reconstruct human cardiac development in 3D. Cardiac mesoderm stage human Cardioid visualizing Phalloidin (grey) and β-catenin (Magenta).
Image Credit: Deniz Bartsch

Writing in ‘Science Advances’ researchers of the University of Cologne describe a key mechanism that controls the decision-making process that allows human embryonic stem cells to make the heart. These discoveries enable better insights into how the human heart forms in an embryo and what can go wrong during heart formation, causing cardiac disease or, in the worst case, embryo termination.

In humans, a specialized mRNA translation circuit predetermines the competence for heart formation at an early stage of embryonic development, a research team at the Center for Molecular Medicine Cologne (CMMC) and the University of Cologne’s Cluster of Excellence in Aging Research CECAD led by Junior Professor Dr Leo Kurian has discovered. While it is well known that cardiac development is prioritized at the early stages of embryogenesis, the regulatory program that controls the prioritization of the development of the heart remained unclear until now. Kurian and his team investigated how the prioritization of heart development is regulated at the molecular level. They found that the protein RBPMS (RNA-binding protein with multiple splicing) is responsible for the decision to make the heart by programming mRNA translation to approve future cardiac fate choice. The study is published under the title ‘mRNA translational specialization by RBPMS presets the competence for cardiac commitment’ in Science Advances.

Researchers find way to treat lung cancer and associated muscle wasting at the same time

Illustration shows depicts treating lung tumors with lipid nanoparticles loaded with follistatin.
Image Credit: Parinaz Ghanbari

Scientific Frontline: Extended "At a Glance" Summary: Dual-Targeted mRNA Therapy for Lung Cancer and Cachexia

The Core Concept: This novel therapeutic approach utilizes specialized lipid nanoparticles (LNPs) to deliver follistatin messenger RNA (mRNA) directly to lung tumors, simultaneously inhibiting cancer growth and reversing cachexia, a severe muscle-wasting syndrome.

Key Distinction/Mechanism: Unlike conventional LNPs, which typically accumulate in the liver following systemic administration, these modified LNPs bind to the blood serum protein vitronectin. The vitronectin directs the LNPs specifically to lung cancer tumors by interacting with integrin receptors that are overexpressed on the tumor surface. Once absorbed, the mRNA instructs the cells to produce follistatin, a protein known to suppress tumor progression and stimulate muscle tissue growth.

Major Frameworks/Components: 

• Lipid Nanoparticles (LNPs): Nanoscale delivery vehicles composed of fatty acids designed to carry genetic material intravenously without degrading.
• Follistatin mRNA: The therapeutic genetic payload that triggers the endogenous production of the dual-action follistatin protein.
• Vitronectin: A naturally occurring blood serum protein that binds to the LNPs and acts as a homing beacon.
• Integrin Receptors: Surface receptors overexpressed on lung cancer cells that interact with vitronectin to facilitate the precise cellular uptake of the LNPs.

Nasal Spray Booster Keeps COVID-19 at Bay

A nasal spray coronavirus vaccine booster helps protect mice from SARS-CoV-2. In this electron microscopy image, viral particles are shown as blue circles.
Credit: CDC/ Hannah A Bullock; Azaibi Tamin

A new coronavirus vaccine guards one body part especially vulnerable to infection: the nose.

Dosing mice with a nasal spray booster recruited an army of immune defenders to both the nasal cavity, where coronaviruses typically enter the body, and the lungs, scientists report in a preprint posted on bioRxiv.org.

Made only of coronavirus spike protein, the vaccine is part of a one-two punch that could one day protect people from infection. Dubbed “Prime and Spike,” the strategy relies on an mRNA coronavirus vaccine injection that primes the immune system to recognize SARS-CoV-2, followed by a nasal spray vaccine that shores up defenses at the mucus membranes.

Such a strategy might offer a way to counter the waning effectiveness of current mRNA coronavirus vaccines, says study author Akiko Iwasaki, a Howard Hughes Medical Institute Investigator at Yale University.

Until now, scientists had not tested nasal vaccines on animals that already had some pre-existing immunity, says Jacco Boon, a virologist at Washington University School of Medicine in St. Louis who was not involved with the new work. “This paper is telling us that the intranasal booster induces a really good immune response in the nose and the lungs,” he says. “It’s a clever strategy, and I hope they test it in people.”

Purdue mRNA therapy delivery system proves to be shelf-stable, storable

The Proceedings of the National Academy of Sciences has published research about a Purdue University virus-mimicking platform technology that targets bladder cancer cells with mRNA therapies. The LENN platform scientists include, from left, Christina Ferreira, Saloni Darji, Bennett Elzey, Joydeep Rakshit, Feng Qu and David Thompson.
Photo Credit: Purdue University /Ali Harmeson

Scientific Frontline: "At a Glance" Summary

• Main Discovery: The LENN (Layer-by-layer Elastin-like Polypeptide Nucleic Acid Nanoparticle) platform successfully delivers mRNA therapies to bladder cancer cells while retaining full biological activity after being freeze-dried into a shelf-stable powder.
• Methodology: Researchers engineered a virus-mimicking dual-layer nanoparticle to condense and protect nucleic acids, then subjected the formulation to lyophilization (freeze-drying) and storage at -20°C to validate its stability and rehydration properties.
• Key Data: The lyophilized samples maintained complete structural integrity and functionality after three days of storage, successfully targeting upregulated receptors on tumor cells without triggering an immune response.
• Significance: This technology overcomes the severe cold-chain limitations of current lipid nanoparticle systems—which often require storage below -45°C—by providing a biomanufacturable, storable powder form that facilitates easier global distribution.
• Future Application: The team is upscaling the system for preclinical evaluation and initiating efficacy and safety studies in mouse models of bladder cancer.
• Branch of Science: Nanomedicine, Pharmaceutical Chemistry, and Oncology.
• Additional Detail: Multiple reaction monitoring (MRM) profiling confirmed that the system utilizes natural entry pathways and avoids immune detection, potentially solving the "redosing" clearance issues associated with traditional viral vectors.

Spliceosome: How Cells Avoid Errors When Manufacturing mRNA

Quality control during splicing: When an error in the precursor mRNA is detected, the spliceosome is blocked, the recruited control factors interrupt the “normal” cycle, and a molecular short circuit causes the spliceosome to disassemble.
Image Credit: © K. Wild, K. Soni, I. Sinning

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers successfully visualized a "blocked" spliceosome at high resolution for the first time, revealing the specific mechanism by which cells detect and discard errors during the mRNA splicing process.
• Methodology: The team utilized cryo-electron microscopy to examine defective spliceosomes purified from the fission yeast Schizosaccharomyces pombe, employing molecular markers to isolate the specific complexes stalled by quality control factors.
• Key Data: The study produced the first atomic-level representation of a discarded spliceosome, demonstrating that a "molecular short circuit" occurs upon error detection to trigger the immediate disassembly of the faulty complex.
• Significance: Elucidating this quality control mechanism is critical for medical science, as splicing errors are a primary cause of hereditary genetic disorders and are strongly associated with neurodevelopmental conditions and cancer.
• Future Application: These detailed structural models provide a foundational blueprint for analyzing molecular malfunctions in splicing-related diseases, which may facilitate the development of targeted therapies for conditions caused by aberrant gene expression.
• Branch of Science: Biochemistry and Molecular Biology.
• Additional Detail: The proteins responsible for this quality control process are conserved from fission yeast to humans, indicating that this error-correction mechanism has remained evolutionarily stable and fundamental to eukaryotic life

Scientists pave the way for fast, cost-effective custom enzyme development

The SMART single-molecule display model, predicted by Alphafold3, shows SpDAAO (red) linked to a puromycin linker (magenta) through puromycin incorporation into the growing polypeptide. The mRNA (gray) is hybridized and chemically joined to the linker, connecting it to its protein, SpDAAO. An auxiliary unit is added using ORC hairpin DNA (blue) with APEX2-scCro fusion protein (green).
Image Credit: Hideo Nakano and Jasmina Damnjanović

Scientific Frontline: Extended "At a Glance" Summary: SMART Method for Custom Enzyme Development

The Core Concept: SMART (Single-Molecule Assay on Ribonucleic acid by Translated product) is an advanced in vitro selection platform designed to accelerate directed enzyme evolution. It significantly reduces the time and cost required to identify superior enzyme variants by tracking them at the single-molecule level.

Key Distinction/Mechanism: Unlike traditional directed evolution, which often requires screening up to 100 trillion candidate variants over several weeks, the SMART system links an enzyme protein directly to its corresponding messenger RNA (mRNA) blueprint using puromycin as a chemical bridge. An auxiliary unit utilizing engineered ascorbate peroxidase 2 (APEX2) detects target enzyme activity by attaching a biotin marker to nearby molecules, allowing for rapid isolation and capture of the successful variants.

Origin/History: Developed by a collaborative research group led by Nagoya University, the Institute of Science Tokyo, and Saitama University, the SMART method builds upon the Nobel Prize-winning strategy of directed evolution. The findings, which demonstrate the system's ability to reduce screening time from weeks to just a few days without the need for specialized equipment, were published in ACS Synthetic Biology.

Scientists help discover new treatment for many cancers

UniSA/CCB Professor Greg Goodall, part of the team that made the landmark discovery.
Photo Credit: Courtesy of University of South Australia 

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers identified the specific molecular mechanism responsible for actively transporting circular RNAs (circRNAs) from the cell nucleus to the cytoplasm.
• Methodology: The study mapped the export pathway and revealed that circRNAs utilize a transport mechanism resembling that of proteins, distinct from the export routes used by other forms of RNA.
• Key Data: Circular RNA possesses a closed-loop genetic structure that renders it inherently more stable and durable in the body compared to linear mRNA, which degrades rapidly.
• Significance: Understanding this transport pathway overcomes a major limitation of current RNA technology, validating circRNA as a robust platform for more effective genetic medicines.
• Future Application: These findings enable the development of a next generation of RNA therapeutics and vaccines with increased potency and longevity for treating cancer and other diseases.
• Branch of Science: Molecular Biology, Oncology, and Pharmacology.
• Additional Detail: The discovery confirms that circRNAs are not cellular byproducts but are actively transported to the cytoplasm to perform critical biological functions.

UC Irvine scientists create powerful enzyme that quickly, accurately synthesizes RNA

“This work shows that enzymes are far more adaptable than we once thought,” says study leader John Chaput, UC Irvine professor of pharmaceutical sciences. “By harnessing evolution, we can create new molecular tools that open the door to advances in RNA biology, synthetic biology and biomedical innovation.”
Photo Credit: Steve Zylius / UC Irvine

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers engineered a novel DNA polymerase, designated C28, that efficiently synthesizes RNA with high fidelity and speed, a capability that natural DNA polymerases are biologically designed to reject.
• Methodology: The team utilized directed evolution within a high-throughput, single-cell screening platform to recombine related polymerase genes, evaluating millions of variants to identify unexpected structural solutions without manually redesigning the active site.
• Key Data: The C28 enzyme contains dozens of specific mutations selected from a pool of millions of variants, enabling it to operate at near-natural speeds while accommodating chemically modified RNA building blocks.
• Significance: This breakthrough overcomes fundamental biological barriers to RNA synthesis, creating a versatile tool that can also perform reverse transcription and generate hybrid DNA-RNA molecules using standard PCR techniques.
• Future Application: The enzyme provides critical functionality for developing next-generation mRNA vaccines and RNA-based therapeutics that require customized or chemically modified RNA sequences.
• Branch of Science: Biochemistry, Pharmaceutical Sciences, and Synthetic Biology.
• Additional Detail: Led by Professor John Chaput and published in Nature Chemical Biology, this research demonstrates that directed evolution can unlock molecular functions nonexistent in nature, such as the ability of a DNA polymerase to transcribe RNA.

Mini-Antibodies Reactivate the Guardian of the Genome

Structure of the DNA-binding domain of a reactivated p53 cancer mutant in complex with a stabilizing DARPin.
Image Credit: Andreas Joerger, Goethe University Frankfurt

Scientific Frontline: Extended "At a Glance" Summary: Mini-Antibodies Reactivating p53

The Core Concept: The p53 protein, widely known as the "guardian of the genome," is a crucial tumor suppressor that is mutated in approximately half of all cancer cases; researchers have engineered miniature antibodies called DARPins to stabilize these mutated proteins and restore their protective function.

Key Distinction/Mechanism: Unlike traditional small-molecule therapies that are constrained to targeting single, specific mutations, DARPins can selectively bind to and stabilize a vast array of different p53 mutants simultaneously. Furthermore, while conventional antibodies strictly target extracellular proteins, this new approach uniquely targets and operates on proteins inside the cell.

Origin/History: Developed by a scientific consortium comprising research groups from Goethe University Frankfurt, Philipps University Marburg, the University of Cologne, and the University of Zurich.

Discovery: plants use “trojan horse” to fight mold invasions

Photo Credit: Gábor Adonyi

UC Riverside scientists have discovered a stealth molecular weapon that plants use to attack the cells of invading gray mold. 

If you’ve ever seen a fuzzy piece of fruit in your fridge, you’ve seen gray mold. It is an aggressive fungus that infects more than 1,400 different plant species: almost all fruits, vegetables, and many flowers. It is the second most damaging fungus for food crops in the world, causing billions in annual crop losses.

A new paper in the journal Cell Host & Microbe describes how plants send tiny, innocuous-seeming lipid “bubbles” filled with RNA across enemy lines, into the cells of the aggressive mold. Once inside, different types of RNA come out to suppress the infectious cells that sucked them in.

“Plants are not just sitting there doing nothing. They are trying to protect themselves from the mold, and now we have a better idea how they’re doing that,” said Hailing Jin, Microbiology & Plant Pathology Department professor at UCR and lead author of the new paper.

Previously, Jin’s team discovered that plants are using the bubbles, technically called extracellular vesicles, to send small RNA molecules able to silence genes that make the mold virulent. Now, the team has learned these bubbles can also contain messenger RNA, or mRNA, molecules that attack important cellular processes, including the functions of organelles in mold cells. 

Tracking delivery: new technology for nanocarriers

Lipid nanoparticles visualized using SCP-Nano technology at the cellular level in lung tissue.
Image Credit: © Ali Ertürk / Helmholtz Munich

How can we ensure that life-saving drugs or genetic therapies reach their intended target cells without causing harmful side effects? Researchers at Helmholtz Munich, LMU and Technical University Munich (TUM) have taken an important step to answer this question. They have developed a method that, for the first time, enables the precise detection of nanocarriers – tiny transport vehicles – throughout the entire mouse body at a single-cell level. This innovation, called “Single-Cell Profiling of Nanocarriers” or short “SCP-Nano”, combines advanced imaging with artificial intelligence to provide unparalleled insights into the functionality of nanotechnology-based therapies. The results, published in Nature Biotechnology, pave the way for safer and more effective treatments, including mRNA vaccines and gene therapies.

Nanocarriers will play a central role in the next wave of life-saving medicines. They enable the targeted delivery of drugs, genes, or proteins to cells within patients. With SCP-Nano, researchers can analyze the distribution of extremely low doses of nanocarriers throughout the entire mouse body, visualizing each cell that has taken them up. SCP-Nano combines optical tissue clearing, light-sheet microscopy imaging, and deep-learning algorithms. First, whole mouse bodies are made transparent. After the three-dimensional imaging of whole mouse bodies, nanocarriers within the transparent tissues can then be identified down to the single-cell level. By integrating AI-based analysis, researchers can quantify which cells and tissues are interacting with the nanocarriers and precisely where this occurs.

Restoring the healthy form of a protein could revive blood vessel growth in premature infants’ lungs

A blood vessel organoid.
Video Credit: Yunpei Zhang and Enbo Zhu, Mingxia Gu Lab

A UCLA-led research team has discovered a molecular switch that determines whether tiny blood vessels in premature infants’ lungs can regenerate after injury. A failure of this repair process is a hallmark of bronchopulmonary dysplasia, or BPD, a serious lung disease that affects babies born very early. It arises from a combination of premature birth, inflammation or infection, and exposure to the high levels of oxygen and breathing support that are necessary to keep these infants alive during a critical period of lung development.

The researchers found that in BPD, the blood vessel cells in the lungs begin producing a shortened, nonfunctional isoform — a version of a protein — called NTRK2, which has been extensively studied in the nervous system but not in the pulmonary vasculature. When this shortened isoform dominates, the lung cannot rebuild the delicate network of tiny blood vessels needed for healthy breathing.

Calorie restriction in humans builds strong muscle and stimulates healthy aging genes

NIH study suggests a small reduction in daily calories is beneficial for wellness.
Photo Credit: rawpixel

Reducing overall calorie intake may rejuvenate your muscles and activate biological pathways important for good health, according to researchers at the National Institutes of Health and their colleagues. Decreasing calories without depriving the body of essential vitamins and minerals, known as calorie restriction, has long been known to delay the progression of age-related diseases in animal models. This new study, published in Aging Cell, suggests the same biological mechanisms may also apply to humans.

Researchers analyzed data from participants in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE), a study supported by the National Institute on Aging (NIA) that examined whether moderate calorie restriction conveys the same health benefits seen in animal studies. They found that during a two-year span, the goal for participants was to reduce their daily caloric intake by 25%, but the highest the group was able to reach was a 12% reduction. Even so, this slight reduction in calories was enough to activate most of the biological pathways that are important in healthy aging.