Elevating drug discovery through access to in vivo models

Mouse in drug discovery research

This paid-for advertorial by Taconic Biosciences appeared in DDW Volume 25 – Issue 3, Summer 2024.

Harnessing the power of sophisticated GEMs and humanized mice is essential to moving research forward.

In the dynamic landscape of drug discovery, the utilisation of high-quality animal models is paramount for success. Among these models, research mice and rats stand out as invaluable resources, facilitating the understanding of disease mechanisms and the development of novel drugs. At Taconic Biosciences, we are dedicated to advancing drug discovery by providing researchers with straightforward access to the most sophisticated research models engineered to meet the highest genetic, health, and quality standards. 

Licensing: facilitating straightforward access to genetically engineered models

Genetically engineered models (GEMs) are mice and rats that have been genetically engineered to include or exclude specific DNA modifications. These genetic changes are designed to make a mouse more accurately recapitulate  human diseases, study gene function, or investigate the effects of new therapeutics. As biomedical research has increased in complexity, GEMs have become indispensable tools for understanding complex biological processes, unraveling disease mechanisms, and developing new therapeutic modalities. Understandably, developing advanced and powerful GEMs requires considerable time and significant financial investment. Consequently, organisations that undertake the custom GEM generation may aim to recoup their investment by distributing the model to academic institutions or for-profit companies, thereby seeking a reasonable return on investment. These models then often have intellectual property (IP) associated with their use and breeding. Therefore, licensing agreements play a crucial role in determining the availability of these models. Before beginning a preclinical research project with a GEM, it is vital that researchers understand the full IP landscape of the model, including where and how the model was developed and if any of the materials or technologies used in the generation have patented or restricted use. Too often, IP prevents researchers from obtaining or using the best-suited model for their research. Taconic simplifies this process by breaking down common licensing barriers through securing and maintaining partnerships with leading academic and commercial institutions to obtain licenses for key genetic modifications, ensuring researchers have access to a diverse range of GEMs for their research endeavours. 

Safeguarding genetic integrity in preclinical research

Genetic integrity in mouse and rat breeding colonies has a direct and fundamental impact on the quality and success of a preclinical research program. Without a robust breeding program that incorporates husbandry best practices, colony refreshment strategies, along with monitoring techniques, critical studies can be undermined by strain contamination, genetic drift, and expression changes. While these challenges are universal in rodent research, small GEM colonies are particularly susceptible. Different mutations, such as randomly integrated transgenes and CRISPR edits, require tailored genetic monitoring. Strain background can have unexpected impacts on the phenotypic expression of certain mutations, yet researchers often lack a comprehensive understanding of the background strain composition of their lines. Taconic applies robust strategies to assess, monitor, and maintain genetic quality in both commercial animal model colonies and customer breeding projects. The best practices we follow include colony refreshment strategies as well as technological solutions such as transgene sequencing, monitoring transgene integrity via copy number and expression testing, and whole genome sequencing (WGS) in inbred strain refreshes or spontaneous mutation identification. To further enhance the quality of a breeding program, Taconic colony management projects utilise the Taconic AWARE™ program, an industry-leading initiative that proactively assesses and scores GEM projects based on parameters such as genetic risk and adverse phenotypes. This scoring system is designed to fulfill the scientific needs of the investigator while considering animal welfare, genetic integrity, and the 3Rs (Replacement, Reduction, and Refinement) of animal research. 

The NOG mouse: The first and most versatile severely immunodeficient mouse model

The NOG mouse is a severely immunodeficient model with unique properties that enhance the engraftment of human cells and tissues compared to conventional immunodeficient mouse models. It is also the base of a flexible platform that includes a variety of next-generation models such as human cytokine transgenics (hIL-15 NOG, hIL-6 NOG, hIL-2 NOG, NOG-EXL), MHC class I knockouts (B2m-NOG), murine Fc gamma receptor knockouts (FcResolv® NOG, FcResolv® NOG-EXL, FcResolv® hIL-15 NOG) and as well as several different types of humanized immune system (HIS) models, as illustrated above in the NOG portfolio infographic. 

A 2024 publication in Veterinary Pathology by researchers from the University of Pennsylvania compared the NOG-EXL from Taconic with the NSG-SGM3 from The Jackson Laboratory, resulting in data that revealed that humanized NOG-EXL mice develop a milder myeloid activation syndrome and live longer compared to humanized NSG-SGM3 mice. Additionally, humanized NOG-EXL mice do not develop mast cell hyperplasia, demonstrating that the NOG-EXL model is better suited than the NSG-SGM3 model for immuno-oncology studies  requiring long-term survival post-humanization. Multiple models from the NOG portfolio are readily available off-the-shelf for researchers to incorporate now into their research programs and move their preclinical studies forward.

Learn more at Taconic.com/ddw

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