Why BRETSA™ Target Engagement Matters for Drug Discovery

Posted on by Michele Arduengo, PhD

Drug discovery researchers face a fundamental constraint in their work to develop safe, effective therapeutics: the vast majority of the human proteome remains inaccessible to conventional small molecule approaches. Proteins without defined binding pockets, those lacking known chemical probes, and protein targets that fail to translate from biochemical assays into cellular models have long been considered out of reach of standard drug discovery screening tools. As Dixit et al. describe, developing biochemical or cellular assays for all genome-encoded targets “is not scalable and likely impossible as most proteins have ill-defined or unknown activity” — these are what the authors call “the dark undruggable expanses” of the proteome [1].

That gap is now narrowing. Promega Corporation recently launched the TarSeer™ BRETSA™ Target Engagement System, a live-cell target engagement platform designed to bring previously challenging targets within reach of early-stage drug discovery.

The Problem: A Translation Gap in Early Discovery

Drug discovery teams regularly encounter a frustrating disconnect. A compound may show strong binding activity in a biochemical assay, only to fail when tested in a cellular environment. Without target-specific cellular assays, which generally aren’t available for poorly characterized proteins, researchers face difficult choices when deciding which compounds to advance through the drug development pipeline.

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A Live-Cell NanoBRET Assay Shines Light on Toxic RNA–Protein Interactions in Myotonic Dystrophy

Posted on by Johanna Lee
How NanoBRET works image.

RNA doesn’t just carry genetic instructions—it also interacts with proteins to regulate nearly every aspect of gene expression, from splicing to translation. When those interactions go awry, the consequences can be devastating. In myotonic dystrophy type 1 (DM1), the most common adult-onset muscular dystrophy, a toxic RNA repeat expansion hijacks a critical protein called MBNL1, trapping it in nuclear clumps called foci. This leads to widespread splicing defects and progressive muscle wasting. But studying these toxic interactions inside living cells—and finding small molecules that can disrupt them—has been a significant challenge.

A recent study led by the Scripps Institute may have a solution. The study introduces a NanoBRET™ assay that can monitor the interaction between the expanded CUG RNA repeats and MBNL1 protein in real time, in live cells. Their findings demonstrate how this platform can be used not only to detect disease-driving RNA–protein complexes but also to identify small molecules that break them apart.

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How Enzymes Are Powering A New Generation of Micro-Robots

Posted on by Anna Bennett
Cute, tiny robot. White body, black features, and blue glowing eyes.

Many consider enzymes the workhorses of biochemistry (move over, mitochondria)—catalyzing reactions, breaking down substrates, keeping the machinery of life humming along. But a growing number of researchers are re-envisioning what enzymes can do. Instead of facilitating chemistry, what if enzymes could steer and even guide tiny robots to a tumor? 

That’s exactly what’s happening in the rapidly expanding field of enzyme-powered microscopic robots (a.k.a “microrobots”). Microrobots are tiny, engineered devices—often smaller than the width of a human hair—built to perform tasks inside the body that would be difficult or impossible at a larger scale, like delivering drugs to a specific tissue. A recent paper published in Nature Nanotechnology by a team of researchers at California Institute of Technology and the University of Southern California offers a particularly elegant example that we highlight below1.

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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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More Than Beer and Cheese: Why Wisconsin Has Always Been Good Ground for Science 

Posted on by Elise Johnson

Challenging Assumptions About Innovation

When people talk about places where science and technology tend to flourish, a few names surface almost immediately. Silicon Valley, Boston, Seattle, Houston. Cities associated with density, competition and speed.

For many people outside the state, Wisconsin still collapses into a short list of associations: beer, cheese, cold winters, maybe a football team. Biotechnology rarely makes that list.

That hesitation usually has less to do with science itself and more to do with assumptions about where innovation is supposed to live. National Wisconsin Day, celebrated February 15, is a good moment to look past those assumptions and consider what Wisconsin has quietly offered for a long time: an environment and culture that is well-suited for scientific advances.

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From Gum Disease to Breast Cancer: An Oral Bacterium’s Unexpected Journey

Posted on by Sara Millevolte

You’re sitting in the dentist’s chair, nodding along to the familiar flossing lecture you’ve been politely ignoring for most of your adult life. Fair enough. It’s hard to get excited about gum health. But it turns out your dentist may have been underselling the pitch.

A study published in January 2026 in Cell Communication and Signaling shows that a common gum disease bacterium can promote breast cancer growth and spread in mice, and the findings hint at a particularly troubling link for people carrying BRCA1 mutations (1). “Floss to help prevent cancer” probably wasn’t on your 2026 bingo card, yet here we are.

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Polar Bears, Shrinking Sea Ice and a Scientific Surprise

Posted on by Kelly Grooms
A polar bear sits on a snow-covered ice floe in the Arctic Ocean, gazing toward the horizon as sunlight filters through clouds over icy water.

When you think about climate change in the Arctic, you might imagine melting sea ice or maybe hungry polar bears. After all, polar bears depend on sea ice to hunt seals, and seals are their main source of energy. The negative effects of decreasing sea ice on polar bear body condition index (BCI), survival and reproduction have been documented in polar bear populations from regions such as the Western Hudson Bay and the Southern Beaufort Sea. So, when researchers started studying the polar bears in Svalbard, Norway (Barents Sea region), which is losing sea ice at a faster rate than any other region, they expected the BCI of those bears would also be declining. Except it isn’t.

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The Science of Slipping… Blame the Molecules!

Posted on by Shannon Sindermann

Whether it’s Home Alone’s booby-trapped icy steps, Bambi learning his legs have zero traction, or an Ice Age chase scene defying gravity, ice has been comedy gold for decades. In real life, the joke lands a little harder (sometimes literally).

Slippery Ice

We all know ice is slippery. The more surprising part is why it’s slippery and how long it took scientists to start agreeing on something closer to an answer. Researchers have long known the surface of ice behaves like it’s wearing a microscopic “wet” layer that lubricates motion. What they’ve argued about for nearly 200 years is what creates that layer in the first place (3,4).

So, let’s treat this like a mystery. Ice is the crime scene. Your dignity is the victim. Here are the main suspects.

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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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