Cell and Gene Therapy

These poss relate to research around cell and gene therapy.

Solving the AAV Titer Challenge: A New Approach to Gene Therapy Workflows 

Posted on by Darcia Schweitzer

For the success of adeno-associated virus (AAV)-based gene therapies, accurate viral titration is non-negotiable. But as interest in AAVs as delivery vectors soars, so does the challenge of getting consistent, reproducible genome titers—a critical hurdle in biologics workflows where speed and standardization are paramount.

Impact of DNase Digestion on Accuracy

A recent peer-reviewed study pinpoints a surprising source of this variability: the DNase digestion, a common step used to remove contaminating DNA. “[DNase digestion]… led to a significant decrease in genome titers for several AAV serotypes,” the authors write,highlighting concerns around workflow reproducibility and data reliability.The research, published in Molecular Therapy: Methods & Clinical Development, demonstrates how different engineered AAV serotypes respond inconsistently to standard DNase treatment, significantly impacting final titer results. These findings are particularly relevant for scientists developing and optimizing cell and gene therapy platforms, where regulatory expectations for analytical precision continue to rise.

This study addresses the challenge of accurately measuring viral titers in engineered AAVs, which have enhanced transduction efficiency but exhibit lower yields when measured using traditional genome titering methods. Specifically, the authors explored the impact of DNase digestion on the stability of engineered AAV capsids that contain peptide insertions. Through a series of rigorous experiments including electron microscopy, quantitative PCR (qPCR) and digital droplet PCR (ddPCR), they found that the heat-inactivation step commonly used following DNase treatment to eliminate free-floating DNA can compromise the integrity of engineered AAV capsids.

Continue reading “Solving the AAV Titer Challenge: A New Approach to Gene Therapy Workflows “

Reprogramming T Cells with DCA: A Metabolic Breakthrough

Posted on by Shannon Sindermann
T cell-based immunotherapies, including CAR-T and TCR-T therapies, have transformed cancer treatment.

T cell-based immunotherapies, including CAR-T and TCR-T therapies, have transformed cancer treatment. T cells are a type of white blood cell that plays a central role in the immune system, recognizing and eliminating abnormal or infected cells. These therapies train T cells to attack tumors; however, a major hurdle remains: most lab-grown T cells fail to persist after an infusion in a patient. Despite transferring millions of tumor-targeting cells, many quickly die off, limiting their effectiveness inside the body. But why?

Continue reading “Reprogramming T Cells with DCA: A Metabolic Breakthrough”

Do Zebrafish Hold the Key to Heart Regeneration? 

Posted on by Shannon Sindermann
Heart regeneration after heart attacks can stop poor health outcomes, read for more research

The human body has an incredible capacity for self-repair. Our skin can regenerate after a small cut, bones can heal after fractures and even the liver can regrow to its original size after 70% is lost or removed (3). However, when it comes to the heart, the story is very different. As Miley Cyrus once sang, “nothing breaks like a heart” – and science agrees. Unlike other organs, the heart has almost no ability to regenerate itself after injuries. In instances like myocardial infarctions, more commonly known as heart attacks, large amounts of cardiomyocytes (CMs)—the cells responsible for heart muscle contraction—are lost and cannot be regenerated, causing the formation of non-regenerative fibrotic scar tissue and, ultimately, decline in heart function (1).  

Continue reading “Do Zebrafish Hold the Key to Heart Regeneration? “

Understanding the Promise of Immunotherapy in Veterinary Medicine

Posted on by Promega

Immunotherapy in veterinary medicine is a rapidly evolving field that leverages the immune system to fight diseases. These therapies are particularly effective in treating various cancers, including lymphomas, mast cell tumors, melanomas, and osteosarcomas. Beyond cancer, immunotherapies are also being explored for their potential in managing chronic inflammatory diseases, such as autoimmune disorders where the immune system mistakenly attacks the body’s own tissues. While traditionally, veterinary treatments have focused on surgery, chemotherapy, and radiation, the advent of immunotherapy offers a more targeted approach, particularly for conditions like cancer.  

This targeted approach not only minimizes collateral damage to healthy tissues but also offers the potential for longer-lasting protection by training the immune system to recognize and fight off recurrence of the disease. The interest in immunotherapies has grown in tandem with advancements in human oncology, leading to a crossover of technologies and methodologies into veterinary applications. 

How Does Immunotherapy Work?

Continue reading “Understanding the Promise of Immunotherapy in Veterinary Medicine”

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.
Continue reading “Silencing the Immunogenicity of AAV Vectors “

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.  

Continue reading “Discovery of Protein Involved in TDP-43 Cytoplasmic Re-Localization Points to Potential Gene Therapy for ALS and FTD”

Addressing the Problem of Dosing in Gene Therapy

Posted on by AnnaKay Kruger

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.

Continue reading “Addressing the Problem of Dosing in Gene Therapy”

Transformative Gene Therapies Greenlit for Sickle Cell Disease

Posted on by AnnaKay Kruger
In sickle cell anemia, red bloods cells elongate into an abnormal “sickled” shape

Sickle cell disease is a debilitating blood disorder that causes recurrent pain crises and severe health effects, and can drastically impact quality of life. Recently, Vertex Pharmaceuticals and CRISPR Therapeutics introduced Casgevy, or exa-cel, a novel form of gene therapy that could radically change the management of sickle cell disease. On the heels of exa-cel’s approval in Britain, this groundbreaking therapy was also recently approved in the U.S.

Continue reading “Transformative Gene Therapies Greenlit for Sickle Cell Disease”

How Does Ozempic Work? The Mechanism of Action of Semaglutide and Other GLP-1 Receptor Agonists

Posted on by Jordan Nutting

In early 2023, a type 2 diabetes medication, semaglutide (brand names Ozempic, Rybelsus), drew huge amounts of attention on social media and in popular culture. The reason? People were getting off-label (that is, not for treating type 2 diabetes) prescriptions of Ozempic to take advantage of one of its common side effects—measurable weight loss.

How does semaglutide and other drugs of its type manage diabetes on a molecular level, and what drives the weight loss effects?

Female leg stepping onto a weigh scale
Continue reading “How Does Ozempic Work? The Mechanism of Action of Semaglutide and Other GLP-1 Receptor Agonists”

Small Molecule Therapies and Immunotherapies: An Introduction to Targeted Cancer Treatments

Posted on by Kelly Grooms

Cancer is a deceptively singular term for hundreds of different diseases. These diseases can affect almost any part of the body.  In the United States, cancer is the second most common cause of death (1). At its most basic level, however, cancer is the abnormal and uncontrolled division of cells resulting from genetic changes in one or more cells.

This prolific cell division is what many standard chemotherapies act upon. These therapies are developed to kill rapidly dividing cells but often don’t discriminate between normal and cancerous cells. In contrast, targeted therapies are designed to interact with (or target) specific pathways, processes or proteins whose abnormal behavior is associated with cancer development and growth. Targeting these abnormal cellular functions can counteract cancer in different ways. They can interfere with tumor growth, carry other drugs into tumor cells or help the immune system find and kill cancerous cells. Targeted therapies can be loosely divided into two categories: small molecule therapies and immunotherapies.

Continue reading “Small Molecule Therapies and Immunotherapies: An Introduction to Targeted Cancer Treatments”