Addressing the Problem of Dosing in Gene Therapy

One key obstacle to crafting effective gene therapies is the ability to tailor dosing according to a patient’s needs. This can be tricky because even if protein production is successful, staying within the therapeutic window is paramount—too much of a protein could be toxic, and too little will not produce the desired effect. This balance is difficult to achieve with current technologies. In a study recently published in Nature Biotechnology, researchers at Baylor College of Medicine investigated a possible solution to this problem, engineering a molecular “on/off” switch that could regulate gene expression and maintain protein production at dose-dependent, therapeutic levels.

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Raising Frogs Takes a Village: Accelerating Amphibian Research at the Marine Biological Laboratory

Sally Seraphin and her students Maliah Ryan (second from right) and Jude Altman (right) work with a Promega Applications Scientist at the Marine Biological Laboratory

Sally Seraphin’s life in the research lab started with rats and roseate terns. Chimpanzees and rhesus macaques came next, then humans (and a brief foray into voles). When she pivoted to red-eyed tree frogs, Sally once again had to learn all kinds of new techniques. Suddenly, in addition to new sample prep and analysis techniques, she needed to get up to speed on amphibian care and husbandry. That led her to the Marine Biological Laboratory (MBL) in Woods Hole, MA.

“It’s a seaside resort atmosphere with experts in every technology you can imagine,” Sally says. “It’s a place to incubate and birth new approaches to answering questions.”

Sally spent the past two summers at MBL learning everything she needed to know about breeding and caring for amphibians. During that time, she also worked closely with Applications Scientists from Promega who helped her start extracting RNA from frog samples.

“The hands-on support from industry scientists is definitely unique to Promega and MBL,” she says. “It’s rare to have a specialist on hand who can help you learn, troubleshoot and optimize in such a finite amount of time.”

Adopting a New Model Organism

Sally uses red-eyed tree frogs to study early stress and developmental timing.
Sally uses red-eyed tree frogs to study early stress and developmental timing. Photo from Wikimedia.

Sally studies how early stress impacts brain and behavior development. She hopes to deepen our understanding of how adverse childhood experiences connect to mental illness and bodily disease later in life. In the past, she studied how factors such as parental absence affected the neurotransmission of dopamine in primates. Recently, she changed her focus to developmental timing.  

“Girls who are exposed to early trauma like sexual or physical abuse will sometimes reach puberty earlier than girls who aren’t,” Sally explains. “And I noticed that there are many species that will alter their developmental timing in response to predators or social and ecological threats.”

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Transforming Forensic Science with DNA from Dust

A ray of sun coming through the wooden shutters, illuminates dust on the inside of a dark room. Close up, selective focus. Vintage background. This image is licensed from Adobe Stock.

In the evolving field of forensic science, a study by Fantinato et al. has opened new avenues in using DNA extraction and analysis to recover important information from crime scenes. Their work, “The Invisible Witness: Air and Dust as DNA Evidence of Human Occupancy in Indoor Premises,” focuses on extracting DNA from air and dust. This novel approach could revolutionize how crime scenes are investigated, especially in scenarios where traditional evidence—like fingerprints or bodily fluids—is scarce, degraded or has been removed from surfaces.

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Elevate Your Research: Exploring the Power of 8-Dye STR Chemistry with the Spectrum Compact CE System

In genetic research, staying at the forefront of technology is crucial. The latest breakthrough in human identification comes in the form of 8-dye Short Tandem Repeat (STR) chemistry. This innovation promises unprecedented precision and accuracy in DNA analysis, revolutionizing the way we approach genetic studies. In this blog post, we’ll delve into the world of 8-color chemistry and explore how it seamlessly integrates with the game-changing Spectrum Compact CE System.

Understanding 8-Dye STR Chemistry

The introduction of 8-dye chemistry expands the capability of STR analysis, enabling researchers to analyze more DNA markers with smaller amplicons, providing more robust data from degraded or inhibited DNA samples.  The performance of the 8-color dye chemistries from Promega on the Spectrum Compact CE System is sensitive, with both chemsitries (PowerPlex® 35 GY System and the upcoming PowerPlex® 18 E System) producing 100% profiles from their suggested inputs down to as little as 62.5 pg of DNA. The 18E system produced 100% profiles down to 31.25 pg of input DNA with minimal signal bleed through and low system noise.

Table showing percent STR profiles generated with decreasing input DNA using the PowerPlex 35GY or PowerPlex 18 E chemistry on the Spectrum Compact CE System
Table showing percent profiles generated with decreasing input DNA using the PowerPlex® 35GY or PowerPlex® 18E chemistry on the Spectrum Compact CE System.
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Custom in vitro Transcription Reagents for Manufacturing RNA Therapeutics

Doctor filling syringe

Research into vaccines based on RNA began decades ago when scientists theorized that they could harness RNA to produce viral proteins within a cell, prompting a protective immune response. RNA vaccine research drew scientists’ attention during the development of SARS-CoV-2 vaccines during the COVID-19 pandemic, which opened the door for research targeting other diseases with RNA-based therapeutics.

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Streamlining Disease Diagnostics to Protect Potato Crops

A potato farmer holds a handful of potatoes. Scientists are working to protect potato crops from disease.
The WSPCP works to provide seed potato growers with healthy planting stock

The mighty potato—the Midwest’s root vegetable of choice—is susceptible to a variety of diseases that, without proper safeguards, can spell doom for your favorite side dishes. Founded in 1913 and housed in the Department of Plant Pathology at the University of Wisconsin-Madison, the Wisconsin Seed Potato Certification Program (WSPCP) helps Wisconsin seed potato growers maintain healthy, profitable potato crops year-to-year through routine field inspections, a post-harvest grow-out and laboratory testing.

While WSPCP conducts visual inspections for various seed potato pathogens, their diagnostic laboratory testing is primarily focused on viruses such as Potato virus Y (PVY), which can cause yield reduction and tuber defects, along with select bacteria such as Dickeya and Pectobacterium species that cause symptoms like wilting, stem rot and tuber decay.

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DNA from a ~20,000-Year-Old Pendant Offers Genetic Picture of Its Owner

The elk tooth is small and ancient, with a crude hole bored through the top. It was likely worn as a pendant, but worn by whom? Was the owner male or female? Where did they come from? Did the pendant indicate their social status, mark a significant accomplishment, was it a gift, or was it worn as an expression of individuality?

Artifacts such as personal ornaments and tools play a pivotal role in helping us understand the migration, behavior and cultures of ancient peoples. To date, this information has stopped short of providing insight into things like the biological sex or genetic ancestry of the individuals who may have worn or used these items, and thus limited our ability to accurately characterize societal roles and behaviors. Recent advances in DNA techniques and technologies, and one little pendant, might be changing that.

gloved hands hold an artifact pendant
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Shifting Gears: Repurposing Instruments for Changing Needs

Sarah Teter operates the Tecan Freedom EVO 150 liquid handler
Sarah Teter operates the Tecan Freedom EVO 150

The thought of an expensive instrument falling out of use and gathering dust on the shelf is enough to bring a tear to any lab manager’s eye. An instrument that once served a key purpose and now functions only as a “paperweight” is a tragic waste of valuable resources. Fortunately, it is sometimes possible to breathe new life into neglected tools and to retrofit or repurpose equipment to meet the new needs that will inevitably arise in a changing lab environment.  

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Left-Handed DNA: Is That Right?

There’s a certain group of people (including this blog post author) who derive no small amount of amusement from seeing stock photos of DNA and pointing out flaws in the structure. It’s even more amusing when these photos are used in marketing by life science companies. The most common flaw: the DNA molecule is a left-handed double helix.

What does that even mean? DNA, like many organic chemicals in biology, is a chiral molecule. That is, it can exist in two structural forms that are mirror images of each other but are not superimposable (enantiomers). Just like your left and right hands are mirror images of each other, the two DNA structures are left-handed and right-handed double helices. The DNA double helix is chiral, because its building blocks (nucleotides) are chiral.

Two DNA helices that are mirror images

It can be challenging, at first glance, to tell whether an image of DNA is left-handed or right-handed. Various helpful hints are available; however, the one that I’ve found easiest to remember is described in a blog post by Professor Emeritus Larry Moran at the University of Toronto:

Imagine that the double helix is a spiral staircase, and you’re walking down the staircase. If you’re turning to the right as you descend, the DNA structure is right-handed; if turning to the left, it’s left-handed. In the image shown earlier, the DNA molecule on the right is a right-handed double helix, while its mirror image is left-handed.

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Circulating Nucleic Acids in Human Biofluids and Liquid Biopsy Research

Several different types of nucleic acids can be found circulating in human biofluids. Fragmented DNA and RNA are now routinely purified from plasma and other bodily fluids. These types of nucleic acids need to be purified from a cell-free fraction of the biofluids to ensure that the isolated nucleic acids are truly circulating and not from intact cells. In this blog post, we will learn a bit more about circulating nucleic acids (CNA) and how they can be used as biomarkers in research.

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