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The Molecular Blueprint for Virus-Resistant Cowpea

Posted on by Anna Bennett

Cowpea (Vigna unguiculata), a humble tan and black legume, is one of the most important food crops in the world. Grown across sub-Saharan Africa, Asia, and parts of the Americas, Cowpea provides protein-rich nutrition for hundreds of millions of people, making it a cornerstone of smallholder agriculture. But cowpea production faces a persistent threat: the cowpea aphid-borne mosaic virus (CABMV), a common virus that can devastate yields across entire growing regions.

A dark background with a wooden spoon holding tan and black beans scattered on the spoon and on the background.

What makes CABMV particularly difficult to combat is how the virus infects its host. Instead of relying on viral translational machinery, the virus hijacks the plant’s systems to replicate. CABMV targets a protein called eIF4E, a translation initiation factor that the plant needs to read its own genetic instructions and produce proteins. The virus produces a protein, VPg, that binds directly to eIF4E and redirects the plant’s translational machinery to produce viral proteins instead. The plant can’t simply get rid of eIF4E. Without it, protein synthesis stalls. So how can cowpea defend itself against a virus that exploits one of its most essential proteins?

A new study published in Agronomy by researchers at the Federal University of Pernambuco, the Federal University of Minas Gerais, and Embrapa Recursos Genéticos e Biotecnologia takes a comprehensive look at this problem from the inside out1. The team characterized all three members of the eIF4E gene family in cowpea  (eIF4E, eIF(iso)4E, and nCBP) across six cultivated varieties (cultivars) with known contrasting responses to CABMV infection. Two of those cultivars (Bajão and IT85F-2687) are resistant to the virus; the other four (Boca Negra, BR14 Mulato, Pingo de Ouro, and Santo Inácio) are susceptible to the virus.

Using a multi-omics approach that combined genomic, evolutionary and structural analyses, the researchers set out to answer a fundamental question: what makes some versions of eIF4E exploitable by the virus, and others not?

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Beyond the Liver: How Liposomal LNPs Are Expanding the Reach of mRNA Delivery

Posted on by Simon Moe

Introduction

Lipid nanoparticles (LNPs) have transformed mRNA delivery. From COVID-19 vaccines to the first approved RNAi therapeutic, ONPATTRO (Patisiran), LNPs have proven their ability to ferry nucleic acid cargo into cells with speed and efficiency (Huang, 2019). Despite this transformation, most clinically deployed LNP formulations share a significant constraint: following intravenous administration, roughly 90% of the injected dose clears to the liver within an hour. If your target is a hepatocyte, that is hardly a hindrance. It’s a serious limitation if you need to reach the spleen, lymph nodes, pancreas or other extrahepatic tissues, all of which are organs of major interest in immunotherapy, vaccine development and metabolic disease research.

A new paper from Pieter Cullis’s laboratory at the University of British Columbia (UBC) offers a structural solution to that problem. Their design, termed a ‘liposomal LNP’, reengineers the architecture of the particle itself to achieve dramatically longer circulation lifetimes and improved transfection in tissues that standard formulations have largely missed.

What are Lipid Nanoparticles?

LNPs enable fast transfection of a wide variety of cells, facilitating the transport of mRNA, DNA and siRNA into cells to induce transient expression in a short period of time (mere hours for mRNA and one to two days for DNA). They are a powerful tool that rose to broad public awareness through their use in COVID-19 vaccines, which delivered spike protein mRNA as cargo. Beyond vaccines, LNPs have been applied therapeutically as the delivery vehicle for ONPATTRO, which treats polyneuropathy of hereditary transthyretin-mediated amyloidosis (Huang, 2019).

The most widely studied LNP formulation, such as the ONPATTRO-like composition, consists of four components: an ionizable lipid, a helper lipid, cholesterol and a PEG-lipid. At physiological pH, the ionizable lipid is neutral and resides in a hydrophobic oil-like core surrounded by a lipid monolayer. This structure is highly effective at transfecting hepatocytes, but its rapid hepatic clearance limits its utility for reaching other tissues.

A Structural Redesign: What Makes the Liposomal LNP Different

Standard ONPATTRO-like formulations have a lipid monolayer surrounding an oil droplet core. The UBC team’s publication reasoned that dramatically increasing the proportion of bilayer-forming lipids, specifically equimolar egg sphingomyelin (ESM) and cholesterol, could fundamentally change what the LNP looks like (Cheng, 2025).

The authors explored various bilayer-to-ionizable lipid molar ratios (RB/I) to see how they modified the structure of the particle. They found that an RB/I of 4 resulted in particles that transition to a true liposomal architecture consisting of a lipid bilayer enclosing an aqueous interior with a solid core suspended inside. Cryo-electron microscopy confirmed that approximately 84% of particles at this ratio adopt this bilayer structure, with the solid core occupying roughly 30% of the interior. LNP sizes across all tested ratios remained in the 40–60 nm range, confirming that the structural shift happens without meaningful changes in particle size.

Why the Structural Change in Liposomal LNP Affects Assembly and Delivery

The liposomal LNP exploits pH-driven structural transitions at both the assembly and delivery stages, explaining how a particle dominated by bilayer lipids can remain transfection-competent.

Assembly: When an ethanol-lipid mixture meets an acidic aqueous buffer (pH 4) containing mRNA, the positively charged ionizable lipid binds the negatively charged mRNA, forming a core complex. This complex acts as a nucleation point for the deposition of ESM/cholesterol bilayer lipid. As pH rises to 7.4 during formulation, ionizable lipids in the outer monolayer shift to a neutral form and migrate inward, expanding an oil droplet core. The mRNA dissociates from the oil core and resides in the aqueous interior where it is protected within the bilayer.

Delivery: After endocytosis, the acidic endosomal environment reverses this process. The ionizable lipids become positively charged again and migrate to the outer surface of the LNP, causing the solid mRNA-containing core to extrude outward from the liposomal bilayer. This positively charged protrusion interacts with the negatively charged endosomal membrane, triggering fusion and releasing the mRNA into the cytoplasm for translation. The authors describe this as a localized “warhead” mechanism—a structural consequence of the bilayer architecture, rather than a simple membrane-disruption event.

Exploring the Performance of the Liposomal LNP

The authors utilized NanoLuc® mRNA as a reporter payload throughout the study. From in vitro transfection efficiency to whole-animal imaging, it allowed the authors to detect differential expression that would have been difficult to detect with less sensitive reporters.

The performance of the Liposomal LNP tells a compelling story. In vitro, the RB/I = 4 formulation matched or exceeded the transfection potency of the ONPATTRO-like composition in Huh7 cells across a wide dose range, while also proving to be the most stable on the shelf. After 63 weeks at 4°C, it maintained greater than 80% mRNA encapsulation with less than 20% size increase, and produced the highest mRNA integrity and translatability of any tested ratio.

SPECT/CT imaging of whole animals with the Liposomal LNP showed a circulation half-life approximately 15-fold longer than the standard ONPATTRO-like formulation, a direct consequence of the bilayer exterior adsorbing roughly half the plasma protein load. This reduced exterior plasma protein load means less macrophage recognition, less clearance and more time in circulation to reach tissues beyond the liver. That improved lifetime in circulation translated into improved tissue access. Ex vivo organ analysis showed 50-fold greater luminescence in the spleen and 150-fold greater in the inguinal lymph node compared to the standard formulation. Meaningful signal was also detected in the pancreas, a tissue rarely reached through conventional LNP formulations. Immunofluorescence confirmed delivery was localized to macrophages at the marginal zone of the spleen and subcapsular sinus of the lymph node.

It is also worth noting that the liposomal morphology held up when tested with the ionizable lipids used in the BNT162b2 and the mRNA-1273 COVID vaccines, suggesting this is a generalizable design.

Expanding Use of NanoLuc® mRNA: UBC RNA and Formulation Core

Throughout this study, NanoLuc® mRNA served as the reporter payload. In vitro, NanoLuc® luminescence normalized to total protein provided a sensitive, linear measure of transfection efficiency across a wide dose range. In vivo, it enabled whole-animal IVIS imaging using the Nano-Glo® Fluorofurimazine substrate, with quantification extended to ex vivo organ homogenates using the Nano-Glo® Luciferase Assay System. NanoLuc® Luciferase sensitivity enabled detecting differential expression in tissues as small as inguinal lymph nodes and the pancreas. Detecting meaningful signal from a lymph node or pancreas can be challenging and thus successful detection demonstrates the exceptional performance of NanoLuc® Luciferase.

The authors synthesized their NanoLuc® mRNA in-house, a capability not universally available to research groups. We have partnered with the University of British Columbia RNA and Formulation Core to close that gap, enabling distribution of NanoLuc® mRNA across the core’s academic and industry network. Researchers who want to investigate LNP delivery, optimize formulations or validate mRNA constructs can now work with the RNA and Formulation Core to acquire NanoLuc® mRNA without the overhead of in-house synthesis. Work from UBC has contributed foundational understanding for LNP formulations, and now through their core they enable NanoLuc® mRNA development for any interested scientist.

Conclusion

The work from UBC demonstrates what becomes possible when mRNA delivery can reach beyond the liver, but the findings are only useful if researchers can access the tools to replicate and build on them. That’s where the UBC RNA and Formulation Core comes in. By partnering with Promega to distribute NanoLuc® mRNA, the Core gives researchers direct access to the same reporter used in this study, without the overhead of in-house synthesis. Whether you’re optimizing an LNP formulation, validating extrahepatic delivery or exploring mRNA constructs for a new application, you can now work with the Core to get started.

Interested in learning more about the UBC RNA and Formulation Core? Explore their website.

Learn more about the full NanoLuc® portfolio.

Citations

Cheng, M.H.Y. et al. (2025) Liposomal lipid nanoparticles for extrahepatic delivery of mRNA. Nature Communications 16, 4135.
Huang, Y.Y. (2019) Approval of the first-ever RNAi therapeutics and its technological development history. Prog. Biochem. Biophys. 46, 313–322.

Piecing Together the Primate Gut Microbiome: Known Residents and Novel Species

Posted on by Anna Bennett

If you’ve read anything about the gut microbiome in the last decade, you’ve probably encountered a familiar setup: researchers collect stool samples, sequence the microbial DNA, and draw conclusions about gut health based on what microbes populate the gut. It’s a practical approach because stool is relatively easy to collect and doesn’t require invasive procedures. But how well does a stool sample represent the health of the entire intestinal tract?

A team of researchers at the Quadram Institute Bioscience and UK Health Security Agency set out to answer this question in primates1. They characterized the intestinal microbiome of cynomolgus macaques, a primate commonly used in biomedical research because of its genetic and physiological similarities to humans. Rather than relying on stool alone, the team collected samples from six distinct regions along the intestinal tract in 24 captive-bred animals ranging in age from 4 to 20 years.

Four hands putting jigsaw puzzle pieces with image of large intestine together.
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Down the Rabbit Hole: The Search for New England’s Disappearing Cottontail

Posted on by Anna Bennett

Connecticut is a small yet ecologically interesting state. Over 85% of the human population lives in cities, yet more than 60% of the land is covered by forest, creating a diverse mix of habitats where wildlife and urban life overlap. In this landscape, bobcats have staged an impressive comeback over the past several decades, reclaiming their role as one of the region’s top predators. But as bobcat numbers rise, a quieter story is unfolding alongside them: the New England cottontail, the region’s only native rabbit, is vanishing.

a brown rabbit facing the camera with grass in the background.
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Before the First Dose

Posted on by Elise Johnson

Kierkegaard observed that one of humanity’s enduring tensions is that while life can only be understood backwards, it must be lived forwards. It’s a truth medicine knows intimately: in the treatment that worked until it didn’t, the resistance that arrived without warning, the moment a doctor has to tell a patient that the drug that was helping has stopped. Not because anyone made a mistake, but because the critical knowledge that would have mattered arrived too late, if at all.

A recent paper from the National Cancer Institute is, in a small but meaningful way, science’s pursuit of that elusive foresight: an understanding that emerges early enough, for once, to change what happens next.

The Elegant Idea

For decades, chemotherapy has worked by brute force, flooding the body with toxins designed to kill rapidly dividing cells. The problem is that rapid division isn’t unique to cancer. Hair follicle cells, gut lining cells and immune cells also divide rapidly, which is why patients lose hair, lose energy and become susceptible to infection. Chemotherapy targets a behavior, but the drug has no way to tell a healthy cell from a cancerous one.

Antibody-drug conjugates (ADCs) change that. Instead of targeting what cancer cells do, they target what cancer cells are. Cancer cells tend to display certain proteins on their surface in far greater numbers than healthy cells do. The antibody is engineered to seek out those proteins specifically. It navigates to its target, binds and waits for the cell to do what cells routinely do: pull it inside. Once there, the cell’s own digestive machinery (the lysosome) breaks down the chemical tether holding the toxin to the antibody, releasing the toxin to kill the cell from within. More than a dozen ADCs have received FDA approval in recent years, and the field is evolving fast.

What the Cell Does Next

But cancer cells don’t simply accept their fate. Even when an ADC delivers its payload perfectly—the antibody finds its target, the cell pulls it inside, the lysosome cuts the tether—a pump embedded in the cell membrane can grab the released toxin and throw it back out before it causes damage.

The delivery worked. The package got ejected anyway.

These pumps—ATP-binding cassette transporters, or more plainly, efflux pumps—are a normal feature of cell biology. Their job is cellular housekeeping, clearing out unwanted or toxic substances before they cause damage. Under the pressure of drug treatment, cancer cells do what life has always done under pressure: the ones best equipped to survive do. The same mechanism that has shaped living things for billions of years now works against the treatment. Not all cancer cells are identical, and the ones that happen to produce more pumps survive while others don’t, gradually shifting the tumor toward resistance.

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Detecting Neuroinflammation in Microglia and Astrocytes

Posted on by Simon Moe

The brain is one of the most complex and fascinating parts of biology. Thankfully, it’s also remarkably good at protecting itself. When exposed to a pathogen, an injury or even misfolded proteins, microglia and astrocytes function as the central nervous system’s (CNS) primary immune defenders. They mount an inflammatory response by releasing cytokines and working to contain the damage. Yet this same system can malfunction or not resolve, which manifests as devastating consequences.

Chronic neuroinflammation is now recognized as a shared characteristic across some of the most common and difficult-to-treat neurological conditions. A 2023 review in Signal Transduction and Targeted Therapy highlighted the dualistic nature of neuroinflammation: while acute responses serve a protective role, chronic or dysregulated inflammatory signaling can initiate and accelerate neurodegeneration, identifying these pathways as priority targets for therapeutic intervention (Zhang et al., 2023). A 2025 review in Science reinforced this view, noting that within Multiple Sclerosis, disease-modifying therapies targeting neuroinflammation have seen the most clinical success (Shi & Yong, 2025). This could suggest applications within neurological conditions where the same inflammatory mechanisms are at work.

Understanding how and where these inflammatory signals originate in the CNS is an active area of preclinical research. One cytokine being actively studied is IL-6. IL-6 is produced by several cell types, including astrocytes and microglia in the CNS. As a key mediator of inflammatory responses, it mediates pro-inflammatory effects through its trans-signaling, which occurs via soluble IL-6 receptors. Dysregulation of this mechanism may contribute to the chronic neuroinflammation seen in several neurological conditions. Characterizing how and when IL-6 is secreted from CNS cells is an important step toward understanding the neuroinflammatory processes underlying these disorders.

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Sequence to Substance: Making the mRNA Therapeutic

Posted on by Shannon Sindermann

mRNA-based therapeutics are being explored across a range of applications, including vaccines, protein replacement and immunotherapies (2).

Before any formulation decisions enter the picture, teams need confidence in the RNA itself: that it is the right sequence, right properties and the right purity to behave predictably downstream. That is where it helps to separate drug substance from drug product. The drug substance is the active ingredient intended to deliver a pharmacological effect, while drug product is the finished dosage form that contains that ingredient (6).

This post focuses on what happens upstream, making the mRNA drug substance before formulation. In practical terms, that upstream work spans choosing an mRNA construct, producing it by IVT, and then purifying and analyzing the product so it has the desired quality attributes (5).

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The Breakthrough Was There All Along

Posted on by Elise Johnson

If you’ve ever played The New York Times game Connections, you know the feeling. You’re staring at a grid of words, knowing the solution is there, but unable to see how the pieces fit together. All you can do is work with the words in front of you. There are no extra clues, no new information coming. The only option is to shuffle, to look at the same information in a different arrangement until patterns begin to appear.

Nothing about the problem changes. Then something about how you see it does.

In 2014, a third-year medical student named David Fajgenbaum checked himself into the emergency room mid-exam. He felt off. By the time anyone understood why, he was in the ICU with multiple organ failure from a disease so rare it wasn’t taught in medical school: Castleman disease. The only approved drug didn’t work. A priest came to his bedside and read him his last rites. He was 25.

Fajgenbaum survived that relapse, and four more after it. As he recounted in a recent episode of NPR’s Radiolab, he understood that chemotherapy was keeping him alive without curing him, and that waiting for a new drug to be developed (a process that typically takes 10 to 15 years and billions of dollars) wasn’t an option he had. So he did something unusual. He started asking his doctors to save his blood samples, and he ran experiments on himself.

What he found was that a specific signaling pathway in his immune system, mTOR, was in overdrive. When he searched the existing pharmacological literature for something that could block it, he found an answer that had been sitting in pharmacies for 25 years. Sirolimus, a drug approved in 1999 to prevent organ transplant rejection, had never been used for Castleman disease. The biology of his disease hadn’t changed. The drug had always existed. The connection simply hadn’t been made.

He took it. It worked. He has been in remission for over a decade.

The detail worth holding onto isn’t the drug or the disease. It’s the instinct. Fajgenbaum didn’t wait for new knowledge to arrive. He looked differently at what already existed.

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Your Media Choice Might Be Designing Your T-Cell Fate

Posted on by Simon Moe

Why Metabolism Matters in T-Cell Expansion

Adoptive T-cell therapies rely on generating metabolically fit, functional cells during ex vivo expansion—but this process often pushes T cells toward highly glycolytic, terminally differentiated states that limit their persistence and therapeutic potential. These metabolic programs begin shifting within hours of activation, therefore understanding early metabolic remodeling is essential for designing culture conditions that support durable, cytotoxic, and memory-enriched T-cell populations.

Researchers at Promega set out to address this challenge by systematically mapping how media composition and activation strength shape T-cell metabolism during the first 72 hours after stimulation. Using a suite of bioluminescent assays, they profiled intracellular energy cofactors, redox balance, and extracellular metabolites across several conditions. This approach revealed distinct, media-driven metabolic states that not only emerged early but also predicted downstream expansion, proliferation, and cytotoxic function.

Their work demonstrates how integrating metabolic profiling into in vitro expansion workflows can provide a more informed framework for optimizing T-cell manufacturing strategies.

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Accelerating Drug Discovery at Grove Biopharma with MyGlo® and ProNect®

Posted on by Promega

At Grove Biopharma, the R&D team is advancing a rational design approach to drug discovery. Their Bionic Biologics™ Platform assembles custom-engineered peptides to target intracellular protein-protein interactions into stable, potent, cell permeable therapeutics. By combining the precision of biologics with the efficiency of synthesizing small molecules, Grove accelerates lead generation and optimization.

Grove’s technology enables targeting key proteins involved in cancer and neurodegenerative diseases for which effective therapeutics have historically been difficult to develop. Their candidate molecules focus on important targets such as the Androgen Receptor splice variant, SHOC2 within the RAS/RAF pathway, the MYC-regulator WDR5, a Tau isoform relevant to Alzheimer’s Disease, and the Keap1-Nrf2 interaction associated with neurodegeneration. These programs have made significant progress and now represent some of the most advanced agents in their pipeline.

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