Decades of Discovery: How the NCI-60 Revolutionized Cancer Drug Screening

The National Cancer Institute’s NCI-60 drug screening panel, comprised of 60 diverse human cancer cell lines, has been a cornerstone in advancing cancer research and drug discovery since its inception in the late 1980s. Developed in response to the need for more predictive and comprehensive preclinical models, the NCI-60 facilitates the screening of thousands of compounds annually, aiming to identify potential anti-cancer drugs across a broad spectrum of human cancers. This article traces the origins, development, and evolution of the NCI-60 panel, highlighting its significant role in advancing our understanding of cancer and therapeutic agents.  

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Celebrating Our 2023 Promega In Action Awardees

Each year, Promega employees are offered the opportunity to receive up to 40 hours paid time off to donate in volunteer service through our Promega In Action program. Providing sustained support of organizations in our community, our employees participate in a wide range of activities.  

In 2023, we awarded 26 individuals who volunteered for 23 different organizations, some bringing along their Promega team members in attendance. From crafting comfort shawls for families of future organ and tissue donors, to volunteering with Meals on Wheels, to journeying to South Africa to deliver charitable donations for children in need, the opportunities to contribute to our community are abundant and impactful.

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Studying Episodic Memory through Food-Caching Behavior in Birds

A black-capped chickadee nibbles on a seed
A black-capped chickadee nibbles on a seed.

Your ability to navigate space and time is anchored in your memory, particularly episodic memory, which catalogues the experiences you have in a given location. This type of memory is shaped by complex neural networks firing within your hippocampus. So how exactly do we store memories of the hundreds of things that happen to us in a day, especially when they unfold in the same settings?

There are theories as to how we form single-shot, or “episodic”, memories, many of which center around the activity of place cells, which light up when you are in a specific environment. The idea here is that, with every event that happens in a place, these cells would shift and fire in novel patterns. Scientists at the Zuckerman Mind Brain Behavior Institute at Columbia University questioned this—while it is known that place cell activity can certainly be affected by experiences, they wondered whether there could be an alternative explanation for episodic recall that wouldn’t require the constant remapping of one’s core memory of a place.

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

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 

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

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 

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 

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

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

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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