Screening Disease-Relevant Biology: How the Endo-GeneScreen Platform Uses Endogenous Protein Detection to Drive Drug Discovery 

Posted on by Amy Landreman

Drug discovery has long grappled with a fundamental tension in high-throughput screening: the more biologically relevant your model, the harder it is to scale. Phenotypic assays in primary disease-relevant cells offer rich biological context, but capturing meaningful, target-specific readouts from these complex systems at screening scale has remained a significant challenge.  In contrast, simpler, more scalable systems are easier to deploy but sacrifice the biological fidelity that makes hits meaningful. A recent study by Samowitz et al. in Nature Communications describes an interesting approach to resolve this tension, the Endo-GeneScreen (EGS) platform. A high-throughput screening system designed to enable scalable detection of endogenous protein levels within disease-modeling cellular contexts. 

A Well-Chosen Proof of Concept 

The authors selected Syngap1 as their proof-of-concept target to develop and demonstrate this approach. De novo mutations in this gene that lead to haploinsufficiency are among the most common genetic causes of sporadic neurodevelopmental disorders, including intellectual disability, autism, and epilepsy. Small molecules that boost SynGAP protein levels back toward wildtype would address the root cause of these disorders rather than managing downstream symptoms. Importantly, Syngap1 function is closely tied to cortical excitatory neurons. Well-validated in vitro and in vivo models for these neurons already exist, creating an integrated system for both discovering new compounds and validating them in the same biological context. That continuity is an important step toward improving the translational relevance of lead molecules coming out of the screen. 

The choice to pursue small molecule modulators of Syngap1 protein levels was also deliberate. Small molecules can be iteratively improved through medicinal chemistry: optimizing brain penetrance, selectivity, and dosing flexibility over successive rounds of synthesis and testing. That iterative potential is central to what makes a phenotypic hit a valuable starting point. 

Building a Screening-Compatible Model Without Sacrificing Biology 

To enable screening at this scale within a biologically relevant context, the authors built their platform around endogenous protein detection in primary cortical neurons. Using standard CRISPR methods, they knocked the small 11-amino acid HiBiT tag into the endogenous Syngap1 locus, creating a Syngap1-HiBiT knock-in mouse strain. Because the tag is inserted at the endogenous locus rather than expressed from a transgene, protein levels reflect native regulation rather than artificial overexpression. During the screen, the HiBiT complementation partner LgBiT is added to the cells during the detection step, reconstituting active NanoBiT® luciferase and generating a luminescent signal directly proportional to endogenous SynGAP protein levels. 

The authors took the model a step further by incorporating a second firefly luciferase (Fluc) reporter. By crossing the HiBiT knock-in mouse with a commercially available transgenic mouse line constitutively expressing Fluc from a ubiquitous promoter, they created an “in-mouse” Dual Luciferase Reporter (DLR) assay. The Nano-Glo® HiBiT Dual-Luciferase® Reporter System was used to sequentially detect first the Fluc signal, reporting on global changes in total protein and cellular toxicity, followed by the HiBiT signal reporting on SynGAP protein levels. This built-in counterscreen is what allows the platform to distinguish compounds that specifically boost SynGAP from those that simply increase all proteins, as well as identifying cytotoxic compounds. Per-well normalization using the median Fluc and HiBiT signals from negative controls further enabled a hit detection algorithm that reduced false positives without sacrificing sensitivity. The assay system leverages the simple add-mix-read workflow, low background, and wide dynamic range that bioluminescent reporter systems deliver at scale. 

From Screen to Validated Hits 

Two independent screens totaling more than 100,000 compounds identified over 40 validated small molecules capable of boosting endogenous SynGAP protein in haploinsufficient neurons. The lead compound, SR-1815, was characterized extensively as a proof-of-concept for the full platform workflow. Beyond the primary DLR assay, the team confirmed SR-1815’s activity using an orthogonal Dot Blot protein assay employing knockout-validated, isoform-specific antibodies against SynGAP, confirming that SR-1815 raised all isoforms proportionally. SR-1815 also demonstrated functional activity, rescuing elevated excitatory synapse strength and neuronal hyperexcitability in haploinsufficient neurons in a genotype-specific manner, consistent with restoring SynGAP’s role in synaptic regulation. 

Early Results and the Road Ahead 

SR-1815 currently faces real pharmacological challenges, notably poor brain penetrance due to P-glycoprotein-mediated efflux and a short half-life, which limits in vivo evaluation until optimized analogs are available. This is expected at this stage, and it is precisely the kind of problem that iterative medicinal chemistry is designed to solve. Interestingly, target deconvolution studies described in a companion publication identified SR-1815 as a multikinase inhibitor that regulates SynGAP levels through alternative splicing, with some targets also implicated in cancer biology. This is an instructive reminder that phenotypic hits can open biological doors well beyond their original indication, and a strong argument for investing in mechanism-of-action work alongside the medicinal chemistry program.

The ~40 additional validated SynGAP-boosting compounds from EGS are now entering early preclinical evaluation, each representing a distinct chemical scaffold and potential therapeutic starting point.

Conclusion 

The Endo-GeneScreen platform is a convincing demonstration that biological relevance and screening scale are not mutually exclusive, but achieving both requires the right technology at the foundation. By combining endogenous HiBiT tagging with the sensitivity and dynamic range of bioluminescence and embedding that within a dual-reporter system that handles selectivity and toxicity in the same assay read, the authors built a platform designed to find the right hits in the right context from the start. Because the HiBiT tag can be knocked into any gene of interest using standard CRISPR methods, and the resulting knock-in mouse line bred with the existing Fluc line, the same infrastructure is immediately extensible to other disease targets, making EGS a modular starting point for physiologically relevant screening well beyond Syngap1. The hits that emerge from this kind of approach carry the credibility of having been found in the right cellular context, jumpstarting next-step translational research efforts.  

To learn more about HiBiT tagging technology for building physiologically relevant model systems, visit: HiBiT Protein Tagging System. 

Tiny Edits, Big Harvests: How a Massive Mutation Screen Could Transform Crop Engineering

Posted on by Johanna Lee

What if we could boost crop yields—not by adding foreign genes, but by tweaking the plant’s own DNA in just the right places?

For decades, plant scientists have known that the noncoding DNA flanking a gene—its promoter and regulatory regions—acts like a volume dial, controlling how much protein the gene produces. Adjusting that dial is the premise behind an approach called quantitative trait engineering (QTE), where CRISPR is used to make small, precise changes to these regulatory sequences instead of inserting entire transgenes. The appeal is enormous: nontransgenic edits face fewer regulatory hurdles and are more likely to gain public acceptance.

The problem? We don’t really understand the rules governing plant promoter architecture. Which nucleotides matter? Where can you cut, insert, or swap bases to crank expression up—or dial it down? Previous attempts to answer these questions have been limited in scale and have rarely uncovered gain-of-function mutations that increase gene expression. Now, however, a new study published in Nature Biotechnology suggests we’re closer to that reality than ever before.

Continue reading “Tiny Edits, Big Harvests: How a Massive Mutation Screen Could Transform Crop Engineering”

Charged Molecular Glues: The Molecular Trojan Horse That Slipped Past Biology’s Toughest Bouncer 

Posted on by Sara Millevolte

The cell membrane is notoriously selective about what it lets in. Charged molecules? Mostly rejected at the door. That’s a problem, because some of the most promising drug targets sit behind that barrier, and reaching them requires chemistry the membrane won’t tolerate. 

Continue reading “Charged Molecular Glues: The Molecular Trojan Horse That Slipped Past Biology’s Toughest Bouncer “

What Counts as Evidence

Posted on by Elise Johnson

This is the third post of three in a series leading up to the 16th annual International Forum on Consciousness, taking place in Madison this May. Hosted by the BTC Institute, Promega and Usona Institute, the forum gathers scientists, philosophers, and practitioners from dozens of different fields to investigate the nature of the mind. This year’s theme, “Unspoken Intelligence,” explores forms of perception and knowing that fall outside conventional cognition.

In 1845, mathematician Urbain Le Verrier calculated where an unseen planet had to be based on irregularities in Uranus’s orbit, wrote a letter to an observatory telling them where to point their telescope, and Neptune was there. He found a planet without ever looking up.

This is what third-person inquiry looks like at its best: observe from the outside, measure what anyone with the right instruments can measure, build a model precise enough to predict what no one has seen yet. Then look. The history of science is full of such moments, equations pointing to phenomena that hadn’t been detected, particles that hadn’t been observed, forces that hadn’t been measured. The method works because it is ruthlessly disciplined about what counts as evidence. The observer is removed, the conditions controlled, and the measurement trusted.

That discipline is not a limitation. It is the engine of over four centuries of extraordinary results. It gave us germ theory, the structure of DNA, and the sequenced human genome. Every time something seemed to resist physical explanation, the method eventually found the mechanism and the method held. The winning streak was long enough that the assumption underneath it stopped looking like an assumption. Outside-in, third-person, measurable evidence stopped looking like one way of knowing. It started looking like the definition of knowing itself.

The assumption felt safe because it had earned its confidence. Digestion, heredity, mental illness, each had seemed to resist physical explanation until it didn’t. The pattern was consistent enough that the method felt inevitable rather than chosen.

Then science turned toward consciousness, and the winning streak entered dangerous territory.

Here is the problem, what philosopher David Chalmers named the “hard problem” of consciousness in 1995.

To understand what Chalmers meant, it helps to start with his own illustration. When you see red, something measurable happens. Light hits the retina. Signals travel along the optic nerve. Specific regions of the visual cortex activate in patterns that neuroscientists can map with increasing precision. All of that is, in principle, fully describable by the third-person, outside-in approach. Given enough time and instruments, you can trace the whole sequence.

What you cannot describe from the outside is what red looks like. The redness of red, that specific quality of experience that exists only in the moment of seeing it, is not in the neural map. No better scanner will find it there, because the felt quality of the experience isn’t a physical thing hiding in the data. It exists only from the inside. The outside measurement, however precise, cannot reach it.

Chalmers used “hard” deliberately, in contrast to what he called the “easy problems” of consciousness: how the brain integrates information, focuses attention, produces behavior. Those are genuinely difficult, but the outside-in approach knows how to go after them. The hard problem is different in kind. It’s the question that remains even after you’ve solved all of the “easy” ones: why does any of it feel like anything at all?

Think of it this way: everything the brain does could, in principle, happen without any felt experience attached. Processing, responding, behaving, all of it could run like a machine in the dark, with no one home. The question Chalmers is asking is why it doesn’t. Philosophers ask it this way: why is there something it’s like to be you, right now, reading this?

No amount of outside-in evidence, however precise, touches that question, not because the science is insufficient but because the method was specifically designed to exclude first-person data. That exclusion was the whole point. It’s what made the outside-in approach so powerful everywhere else.

With consciousness, the method’s central design decision runs into a question it wasn’t built to answer: how do you study first-person experience when your method was built to exclude first-person data?

Continue reading “What Counts as Evidence”

A Historic Milestone for PROTAC Research: What Vepdegestrant’s FDA Decision Means for Drug Discovery

Posted on by Michele Arduengo, PhD

Protein degrader research has yielded its first approved therapeutic for specific breast cancer patients: Vepdegestrant received FDA approval on May 1, 2026 (1). Vepdegestrant is an oral PROteolysis TArgeting Chimera (PROTAC) that targets the estrogen receptor for degradation in breast cancer patients with ESR1-mutated ER+/HER2– advanced breast cancer (2) produced by Arvinas, Inc. in collaboration with Pfizer Inc.

A Different Kind of Drug Development

Targeted protein degraders (or PROTACs) have opened new possibilities in drug discovery research. Instead of inhibiting protein function or interaction, degraders cause the removal of the target protein itself. Traditional small molecule drugs work by binding a protein to inhibit it or block function, and they must remain bound to work. That means that the target protein should be well-characterized in terms of binding and activity sites, and the drug must bind specifically only to the target protein. In contrast, degraders only need to bind long enough to recruit cellular protein degradation machinery to the target protein, and the method does not rely on an accessible and specific binding site on the target protein. Once degradation occurs, the degrader is released and can engage with the next target.

The approval of vepdegestrant is a landmark moment for the entire TPD and induced proximity field, demonstrating that it is possible to rationally design molecules whose pharmacology is categorically distinct from traditional drugs, relying on a catalytic rather than occupancy-driven mechanism of action.  More importantly, this translates to meaningful clinical outcomes in patients. —Dr. Kristin Riching, Promega R&D Scientist

The first peptide-based PROTAC was described in 2001 in the laboratories of Craig Crews and Ray Deshaies (3), but translating the concept into orally bioavailable, clinically viable molecules took nearly two decades, using tools that did not exist when the field began. More than 40 PROTAC degraders have now entered clinical trials (4), with vepdegestrant the most advanced, supported by Phase 3 data from the VERITAC-2 trial demonstrating statistically significant improvement in progression-free survival in ESR1-mutant patients. That progress required solving a measurement problem as much as a chemistry one: how do you quantify target protein degradation at endogenous levels, with enough sensitivity and throughput to drive a screening campaign? CRISPR-engineered protein tagging combined with the small bioluminescent reporter tag, HiBiT solved that problem, providing a sensitive, HTS-compatible readout of endogenous target levels without relying on laborious, artifact-prone western blots. Critically, HiBiT also enabled researchers to watch target protein degradation unfold in real time in living cells.

“Seeing it happen in real time, frankly, may have been what convinced many people that the modality had genuine merit.”
—Dr. Kristin Riching

Developing a PROTAC is not like developing a traditional inhibitor. Success requires successful completion of a complex cascade of cellular events: the molecule must enter the cell, engage the target protein and the E3 ligase simultaneously, form a productive ternary complex in the right geometry, trigger ubiquitination, and drive proteasomal degradation, all while competing with cellular noise that can blunt each step. “PROTACs are large molecules, so they are often not very permeable,” Riching explains. “They also need to simultaneously engage both the target and the E3 ligase machinery, but they need to do so in a productive geometry that leads to ubiquitination, which is not easily predicted. In cells, many compounding factors can limit activity, making it difficult to identify which parameters most need improvement. Event-driven modalities like PROTACs rely on robust tools to tease apart each mechanistic step to aid SAR optimization.”

Getting that data means adopting a screening framework built around mechanistic understanding of the full degradation cascade from the earliest stages of optimization, while preserving the native biology and the stoichiometric relationships that govern degradation efficiency. It also means going beyond endpoint measurements. Knowing whether a target is degraded is a starting point; knowing how fast, how completely, and how durably it degrades is what distinguishes a development candidate from a dead end. Riching’s research has shown that different proteins in the same family can respond to the same PROTAC with dramatically different kinetic profiles (5,6), which is a distinction that endpoint assays cannot capture, and one that can determine which compounds are worth advancing.

What’s Next after Vepdegestrant?

The approval of Vepdegestrant validates more than just a single drug, it validates the PROTAC drug category and the tools and methods that enabled it. For researchers working on next-generation degraders, the signal is clear: the modality works. Now the question is how far we can push it.

Riching points to E3 ligase diversity as the field’s most pressing unresolved problem. “The greatest challenge will be expanding beyond the two E3 ligases — CRBN and VHL — that have driven most PROTAC progress to date,” she says. “We don’t yet fully understand the scope of targets accessible through these ligases, but it stands to reason that additional ligases will be necessary to unlock a larger portion of the degradable proteome. Their broad distribution also limits opportunity for tissue-selective targeting. Developing the tools and chemistry to recruit a wider repertoire of E3 ligases remains one of the most important unsolved problems the field faces.”

Beyond ligase diversity, the field is expanding its conception of what a degrader can be. Molecular glues, LYTACs, and other induced proximity strategies are broadening the range of accessible targets — including extracellular and membrane-bound proteins that sit outside the reach of classical PROTACs. Each new modality brings its own characterization challenges, and the same principle holds: understanding mechanism at the cellular level, early and rigorously, is what separates the compounds worth advancing from those that look promising in a tube.

The approval of vepdegestrant is a landmark. But researchers working in this space know it is a beginning as much as it is a culmination — proof that the approach is sound, and a starting line for everything that follows.

Read more about Innovative Imaging Solutions for Targeted Protein Degradation on our website.

Literature Cited

  1. Arvinas, Inc. Arvinas Announces FDA Approval of VEPPANU (vepdegestrant) for the Treatment of ESR1m, ER+/HER2– Advanced Breast Cancer Accessed: May 5, 2026 
  1.  Arvinas, Inc. (2025) Arvinas Announces FDA Acceptance of the New Drug Application for Vepdegestrant for the Treatment of ESR1m, ER+/HER2– Advanced Breast Cancer. August 8. Accessed: April 27, 2026.  
  1. Sakamoto, K.M. et al. (2001) Protacs: Chimeric Molecules that Target Proteins to the Skp1-Cullin-F Box Complex for Ubiquitination and Degradation. Proc. Natl. Acad. Science USA 98, 8554-–9. Accessed: May 4, 2026. 
  1. Chen, S. (2026) Protein Degraders (PROTACS & Molecular Glues) in 2026: The Emergining Challenge to Traditional Drug Development Accessed: May 5, 2026 
  1. Riching, K.M et al. (2018) Quantitative Live-Cell Kinetic Degradation and Mechanistic Profiling of PROTAC Mode of Action. ACS Chem. Biol. 13, 2758–70. Accessed: May 4, 2026 
  1. Riching, K.M. et al.  (2022) The Importance of Cellular Degradation Kinetics for Understanding Mechanisms in Targeted Protein Degradation. Chem. Soc. Rev. 51, 6210–6221. 

This article was written with AI assistance.

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.

The Filter You Didn’t Choose

Posted on by Elise Johnson

This is the second post in a series leading up to the 16th annual International Forum on Consciousness, taking place in Madison this May, hosted by the BTC Institute, Promega and Usona Institute. The Forum gathers scientists, philosophers, and practitioners from dozens of different fields to investigate the nature of the mind. This year’s theme, “Unspoken Intelligence,” explores forms of perception and knowing that fall outside conventional cognition.

When she thought about a dog, she saw a dog, more specifically, every dog she had ever encountered, cycling through her mind like a card catalog with pictures attached. She assumed everyone did this. When she discovered they didn’t, that most people access something more like an abstract concept hovering somewhere between language and image, she was genuinely surprised. Temple Grandin had always known her mind didn’t work the way people expected. What she didn’t know, until she was an adult, was the specific shape of the difference.

Most of us know this story, or one like it. We understand that some minds filter experience differently, but the science on this doesn’t stop where the conversation usually does.

For most of its history, the field that mapped minds like Grandin’s looked at those that didn’t fit the available systems and concluded the minds were broken. (It didn’t ask whether the systems were.) More recently, the conversation has been reframing those minds not as deficient but as different.

For many people, that reframing has been transformative, changing how educators teach, how clinicians diagnose, and how workplaces are designed. We are now more familiar with alternative cognitive profiles such as autistic pattern recognition (like that experienced by Grandin), ADHD-associated divergent thinking, and the hyper-focused depth of what researchers call monotropic attention. These are not broken versions of normal cognition. They are different architectures, each with genuine capabilities that other minds aren’t built to produce.

The terms most commonly used to describe these differences, neurotypical and neurdivergent, are useful shorthand but they describe a binary the underlying biology doesn’t support. Cognitive traits distribute across a population the way most biological traits do. “Neurotypical” minds are simply closer to the statistical center. What we call “neurodivergent” can be better understood as the part of that population that differs visibly enough from the statistical center to make the variation impossible to ignore.

Continue reading “The Filter You Didn’t Choose”

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.
Continue reading “Piecing Together the Primate Gut Microbiome: Known Residents and Novel Species”

The Body Already Knows

Posted on by Elise Johnson

This is the first post in a series leading up to the 16th annual International Forum on Consciousness, taking place in Madison this May, hosted by the BTC Institute, Promega and Usona Institute. The Forum gathers scientists, philosophers, and practitioners from dozens of different fields to investigate the nature of the mind. This year’s theme, “Unspoken Intelligence,” explores forms of perception and knowing that fall outside conventional cognition.

There’s a quote that travels well in some intellectual circles:

You don’t have a soul. You are a soul. You have a body.

There’s something genuinely relieving about that idea. It locates the real you somewhere above the fray, untouched by the body’s demands and indignities, the consciousness that thinks and persists while the body handles the inconvenient work of being hungry and tired and sick. The thinking part is what counts.

Plato thought something similar. So did Augustine. As did Descartes. Kant, too. The idea that the thinking self is separate from and superior to the body is Western civilization’s default setting.

It sounds like wisdom. It is also, I’ve come to think, exactly the wrong way to understand what we are.

Here’s a different text, one most millennials can recite from memory. In the opening verse of “Lose Yourself,” Eminem rattles off a visceral catalog of physical symptoms: sweaty palms, weak knees, heavy arms, vomiting. The body staging a complete revolt while the mind tries to execute a plan, until the moment on stage when the mouth opens and nothing comes out. The mind wanted to perform, but the body said no.

Nobody who has memorized those lyrics thinks of them as a description of embodied cognition. They file it under music, or nostalgia, or just a song they played too loud in a car they didn’t own. But the nervous system doesn’t care what you call it, because the body doesn’t catalogue in words.

This is the thing the soul-body quote gets wrong: the body isn’t a vehicle the self rides around in. It’s already thinking, already keeping score, already running a process the mind is only partially aware of. The question is what to do about that.

Continue reading “The Body Already Knows”

Stolen Chloroplasts and the Chrysalis of Complex Life 

Posted on by Elise Johnson

Despite its many mysteries, a chrysalis is one of the most familiar transformations in nature. We know what goes in. We know what comes out. For a long time, what happened in between was essentially invisible to us. Not because we weren’t curious, but because the mechanism was sealed inside something the size of a thumbnail, and we had no way in.

This same invisibility exists on a much older and much larger scale.

Sometime around two billion years ago, a cell swallowed a bacterium and, instead of digesting it, kept it alive inside itself. This process, called endosymbiosis, is arguably the single most consequential event in the history of complex life. The bacterium became a permanent resident, and over billions of years of co-evolution, it became something else entirely: the mitochondria that power every complex cell on earth. Without it, the living world as we know it doesn’t exist.

Scientists have known for decades that this kind of cellular acquisition had to have occurred. What has proved harder to explain is not that it happened, but how it started. What did the earliest molecular steps actually look like from the inside?

In the ocean, there is a microscopic single-celled organism called Rapaza viridis. It hunts algae by propelling itself through the water on whip-like appendages called flagella. That hunt may be showing us the beginning of a modern endosymbiosis: the same process that gave every complex cell its mitochondria and every plant its chloroplasts.

Continue reading “Stolen Chloroplasts and the Chrysalis of Complex Life “