AI in the Research Lab: Where We Are, and Where We’re Going

Posted on by Promega

This guest blog post is written by Poncho Meisenheimer, Vice President of Research and Development.

Poncho Meisenheimer is the Vice President of Research and Development at Promega Corporation.

I got into an argument with ChatGPT this morning.

That’s not unusual. I argue with ChatGPT a lot. In fact, that’s usually my goal.

As a scientist and a leader, it’s important to pressure-test my ideas. I need to account for biases, identify limitations, and strengthen weak points. Large language models like ChatGPT have given me a powerful tool in my pocket to become a better version of myself.

The advent of generative artificial intelligence has changed our world. We can’t keep doing things the way we did even only a year ago.

Promega is embracing AI. Every department is finding groundbreaking and responsible ways to deepen their impact using our ChatGPT enterprise license. As the Vice President of Research and Development, I have been working with our scientists to think beyond simple queries and imagine new horizons we can explore with these tools. 

Make no mistake: I don’t think that ChatGPT and other AI tools can, will or should replace human scientists. Instead, they will empower all scientists to ask more ambitious questions and uncover new answers. They will upend our current paradigm about what science is and how it operates, and will help us build an even deeper understanding of the world around us.

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Silencing the Immunogenicity of AAV Vectors 

Posted on by Jordan Nutting

Recombinant adeno-associated viral (AAV) vectors are an appealing delivery strategy for in vivo gene therapy but face a formidable challenge: avoiding detection by an ever-watchful immune system (1,2). Efforts to compensate for the immune response to these virus particles have included immunosuppressive drugs and engineering the AAV vector to be especially potent to minimize its effective dosage. These methods, however, come with their own challenges and do not directly solve for the propensity of AAV vectors to induce immune responses.  

A recent study introduced a new approach to reduce the inherent immunogenicity of AAV vectors (2). Researchers strategically swapped out amino acids in the AAV capsid to remove the specific sequences recognized by T-cells that elicit the most pronounced immune response. As a result, they significantly reduced T-cell mediated immunogenicity and toxicity of the AAV vector without compromising its performance.  

Read on to get more of the study details, which include the use of NanoLuc® luciferase and Nano-Glo® Fluorofurimazine In Vivo Substrate for in vivo bioluminescent imaging of the AAV variants’ distribution and transduction efficiency in mice. 

A teal colored ribbon model of a AAV virus capsid floats against a black background.
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Discovery of Protein Involved in TDP-43 Cytoplasmic Re-Localization Points to Potential Gene Therapy for ALS and FTD

Posted on by Kelly Grooms
A mouse stands on test tubes next to graphic of DNA double helix.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal and rapidly progress as neurodegenerative diseases. While inherited mutations can cause both conditions, they mostly appear sporadically in individuals without a known family history. Despite affecting different neurons, both diseases share a common hallmark: the pathogenic buildup of abnormal nuclear TAR-binding protein 43 (TDP-43) in the cytoplasm of affected motor neuron cells. Current theories propose that this cytoplasmic re-localization triggers toxic phosphorylation and fragmentation of TDP-43. Concurrently, a decrease of TDP-43 in the nucleus diminishes TDP-43-related physiological nuclear functions, contributing to the diseases’ progression (1).

Although this cytoplasmic accumulation of TDP-43 plays a significant role in the pathogenesis of ALS and FTD, the cellular mechanisms involved in the re-localization of TDP-43 to the cytoplasm is not known (2). A team of Australian neuroscientists led by Dr. Lars Ittner believe that they have found part of the answer for sporadic forms of the diseases. They identified novel interactions between pathogenic or dysfunctional forms of TDP-43 and the 14.3.3ɵ isoform of the cytoplasmic protein 14-3-3. By targeting this interaction with an AAV-based gene therapy vector, they were able to block and even partially reverse neurodegeneration in ALS/FTD mouse models.  

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Celebrating 10 Years of Innovation: Introducing the CSCB-Promega Innovation Fund 

Posted on by Riley Bell

For the past decade, Promega has supported cutting-edge research through the CSCB-Promega Innovation Award. Now, as we mark 10 years of collaboration with the Chinese Society for Cell Biology (CSCB), the Award is being converted into the CSCB-Promega Innovation Fund.  

The CSCB, founded in 1980, is one of the leading scientific organizations in China. Dedicated to fostering educational opportunities and innovation, the CSCB organizes conferences, publishes journals, promotes research collaborations, offers training for students and young scientists, and educates the general public on cell biology and biomedicine. 

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A Silent Killer: Tracking the Spread of Xylella fastidiosa 

Posted on by AnnaKay Kruger
Olive tree infected with X. fastidiosa
Olive tree infected with X. fastidiosa

Thought to have arrived in Italy on a plant imported from Costa Rica in 2008, the plant pathogen Xylella fastidiosa was first detected there in 2013. Its subsequent unchecked spread resulted in the loss of millions of olive trees across Southern Apulia, a region in Italy responsible for the production of roughly 12% of the world’s olive oil (5). The pathogen moved swiftly and, to date, a total of 20 million olive trees have been infected across Europe.  

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An Introduction to Lyophilization: Process, Benefits & Possibilities

Posted on by Sara Millevolte
Amber glass bottle filled with lyophilized beads sitting on a lab bench.

Lyophilization is a process designed to remove water from a sample or product through a controlled freezing and vacuum application. The method leverages the triple point of water, where solid, liquid, and gas phases coexist under specific temperature and pressure conditions. The result is a room temperature stable product that is much lighter than the original sample or product.

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Discovering Cyclic Peptides with a “One-Pot” Synthesis and Screening Method

Posted on by Jordan Nutting

In the evolving landscape of drug discovery, cyclic peptides represent an exciting opportunity. These compounds offer a unique balance of size and specificity that positions them to bridge the gap between small molecule drugs and larger biologics like antibodies.

However, most cyclic peptides demonstrate low oral bioavailability: they are digested in the stomach before they can enter the bloodstream, or they’re not absorbed into the bloodstream by the gastrointestinal tract and can have little therapeutic effect (1). Biologics face a similar challenge and are administered intravenously rather than with a more convenient pill form.

A 384 well plate next to a collection of pills of different sizes and shapes.


To address the challenge of low oral bioavailability of cyclic peptides, a team from the Ecole Polytechnique Fédérale de Lausanne in Switzerland developed a “one-pot” method to synthesize a diverse library of cyclic peptides, which they then screened for stability, activity and permeability (1). Their method, which was published December 2023 in Nature Chemical Biology, streamlined the process of identifying and optimizing cyclic peptides and marked a substantial improvement from their earlier studies, where the developed cyclic peptides exhibited almost no oral bioavailability (%F). Using this new method, the team successfully developed a cyclic peptide with 18%F oral bioavailability in rats.

This blog covers the details of this study as well as a brief background on cyclic peptides.

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SLIM Chances: Upside-down, but not Out on the Lunar Surface

Posted on by Shannon Sindermann
The lunar surface

The moon has perpetually been a beacon of curiosity to humankind, always in the sky urging us to look up and beyond. In the mid-20th century, this fascination sparked a historic rivalry between the United States and the Soviet Union, known as the Space Race. This era was marked by extraordinary milestones: satellites orbiting Earth, humans venturing into space and the landmark event of a man setting foot on the moon – a moment etched in history with the phrase, “One small step for (a) man, one giant leap for mankind.” It was an era where the impossible became possible – though some still question if it was a monumental human achievement or an elaborately crafted façade.

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Connecting Synaptic Gene Polymorphisms to Parkinson’s Disease

Posted on by Kendra Hanslik
alt="synapse"

Neurodegenerative disorders represent a significant and growing concern in the realm of public health, particularly as global populations age. Among these, Parkinson’s disease (PD) stands out due to its increasing prevalence and profound impact on individuals. Characterized by the progressive degeneration of motor functions, PD is not just a health challenge but also poses substantial socio-economic burdens. While the etiology of Parkinson’s disease is far from simple, current research efforts elucidating its causes, mechanisms, and potential treatments illustrate the critical nature of this neurodegenerative disorder in today’s healthcare landscape.

In the clinic, Parkinson’s disease is often diagnosed as either sporadic or familial. Familial PD has a clear genetic basis, typically passed down through families, while sporadic PD, comprising about 90% of cases, occurs in individuals without a known family history of the disease. The exact cause of sporadic PD is not fully understood but is believed to be due to a combination of genetic predispositions and environmental factors. In contrast, the factors involved in familial PD are more thoroughly understood, offering insights into the molecular mechanisms underlying PD pathogenesis.

Polymorphisms and Parkinson’s Disease Susceptibility

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How Avian Influenza Crosses Species

Posted on by Johanna Lee

Avian influenza, commonly known as bird flu, has become an increasingly severe public health issue. According to the CDC, the frequency of avian influenza outbreaks and diversity of virus subtypes have increased significantly in the past decade. In 2022, there were reports of sporadic H5 virus infections in mammals across several U.S. states, Canada, and other countries. Affected animals included fox kits, bobcats, coyote pups, raccoons, skunks, mink, and even seals. Human cases of H5N6 and other subtypes following poultry exposures were reported in China, with several cases resulting in severe or critical illness and death.

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