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A team at the Technical University of Munich have created a reporter gene technology that permits longitudinal monitoring of transgene expression in rodents. Developed through the Transgene Track Challenge, sponsored by GSK and Novartis, this system has the potential to reduce animal use in preclinical studies of cell and gene therapies and provide dynamic, real-time data on their biodistribution and activity. We are continuing to support the team in bringing the imaging system to the preclinical research market, increasing access to this technology to reduce animal use and improve research quality.
"Our goal is to make gene and cell therapy development more efficient, ethically responsible, and translatable. By visualising therapeutic cells and vectors in living animals, we can obtain richer data with far fewer animals – helping to move promising therapies towards patients faster. Reducing animal use while improving data quality is a true win–win for science and society. The collaboration with the NC3Rs and the sponsors GSK and Novartis through the CRACK IT Challenge was highly motivating, and we are grateful that the NC3Rs is now supporting the transfer of our reporter gene system to early adopters of the technology."
– Volker Morath, Lead Scientist at Technical University of Munich
About the technology
Assessing the biodistribution and effectiveness of gene and cell therapies, such as adeno-associated viruses (AAVs) and chimeric antigen receptor (CAR)-T cells, typically requires large numbers of animals. A single preclinical biodistribution study can comprise 40 to 60 mice and currently the animals are culled to obtain the required data. These in vivo studies also often have significant variability and do not provide information on the temporal localisation of the gene therapy, either within the target tissue or off-target effects in other organs.
Working with GSK and Novartis, we set the Transgene Track Challenge to develop a non-invasive imaging technology to track the biodistribution and efficacy of cell and gene therapies in vivo. The funded team developed DTPA-R, a Positron Emission Tomography (PET) reporter gene system. The technology uses a surface-expressed binding protein that interacts with a radioligand detectable by PET imaging, allowing the therapy to be tracked in the same animal throughout a study. Longitudinal data collection provides earlier readouts on treatment efficacy and the proliferation and migration of treated cells. This shortens study durations, improves the quality of the data and reduces the overall number of animals required. Having a reliable method that supports comparison of biodistribution data across species could eliminate the need to repeat experiments in multiple species, further reducing animal use. Beyond preclinical applications, the technology could be adapted for clinical translation, making it possible to track advanced therapy medicinal products for safety monitoring in humans.
Find out more about this work
Paper published in Nature Biomedical Engineering: Membrane-anchored anticalin enables PET imaging of transgene expression in vivo.
Learn more about the Transgene Track Challenge.