MISSION & VISION
How GET-IN tackles critical gene therapy technology & knowledge gaps
Tackling critical knowledge gaps
The aim of GET-IN is to address significant knowledge gaps that currently hinder the widespread adoption of gene therapies. This involves optimization of scalable up-stream and down-stream processes, which includes enhancing the production through bioengineering and developing industry-standard biomanufacturing practices. Additionally, GET-IN aims to discover novel, safe, and efficacious gene editing tools broadly applicable, which will be combined with innovative delivery methods. GET-IN will develop cutting-edge organ-on-chip (OoC) technology that allows for the evaluation of efficacy, target tissue specificity, and toxicity in humanized models, surpassing current animal model standards.
Training next-generation innovators
GET-IN's 10 doctoral candidates will receive extensive training in the gene therapy field, which will prepare them well for the highly competitive job market. Moreover, they will be able to contribute to ground-breaking innovations in the field of gene therapy, such as viral vector production, design of experiments, quality by design, digital twin simulation, CRISPR genome editing, and organ-on-chip engineering. The PhD projects are complementary and interconnected, and they include industrial internships and innovative training modules. The candidates become part of a broader network that comprises both academic and industrial leaders.
GET-IN brings together gene therapy innovators from academia and industry. By combining cutting-edge research with industry-standard bioengineering practices, standardization, and optimization of manufacturing processes, GET-IN aims to provide practical solutions to real-world problems. Early adoption of GET-IN's innovations will help to improve market access of novel gene therapies.
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Gene therapy product development presents a significantly higher level of complexity compared to traditional drug and antibody discovery paths. Standardizing and controlling the process becomes more challenging, as it requires in-depth optimization of manufacturing approaches, cost management, and quality control procedures specific to each product. Together with the complex and demanding purification process the current gene therapy production process is overall impractical, difficult and cost-ineffective to scale. To meet the increasing demand, it is crucial to develop new production methods while addressing various critical obstacles related to processes and technologies. Furthermore, the lack of efficient and customized analytical methods hampers downstream processing, hindering accurate, rapid, and adequate analysis
The advancement of genome editing approaches following the identification of CRISPR-Cas opens unprecedented avenues for human health. A first landmark FDA approval is on its way to treat hematopoietic disorders by ex vivo gene editing of autologous stem cells. The next big hurdle to be taken is moving forward in vivo gene editing to tackle additional diseases. In vivo editing requires even more stringent safety profiles of the applied gene editors, alongside considerable upscaling to reach clinical effectiveness for a given disease. In general, transient delivery of CRISPR-Cas machinery favors on-target editing with minimal off-targets. Additionally, gene editing tools that abolish the need for double strand DNA breaks, such as base and prime editing, have reported improved safety profiles. These editors however require advances in delivery systems to accommodate their large cargoes. GET-IN will mine and investigate alternative, smaller CRISPR-Cas derived gene editors, as well as develop and optimize novel delivery systems for genome editing therapies with a focus on transient but efficient delivery (‘hit & go’).
The translational gap between in vitro and preclinical in vivo studies, and application in clinical trials is a major challenge in gene therapy, and delays patient access to safe and effective therapies. Our understanding of gene therapeutic approaches today is largely based on in vitro assessment in conventional 2D-layered cells. There is a substantial discrepancy between the comprehensive insights on subcellular processes gained in these 2D models, as to how they translate at the tissue and organ level. Animal models are used, partially resembling human physiology, but these come with their own drawbacks, rendering their predictive value debatable and limiting translatability. GET-IN aims to tackle this gap by implementing human organ-on-chip models in the gene therapeutic discovery pipeline.
DOCTORAL PROJECTS IN GET-IN
The GET-IN network (Gene Therapy Innovation Training Network) will address these challenges through game changing innovations in viral vector production, design of experiments, quality by design, digital twin simulation, CRISPR genome editing and organoid-on-chip engineering, while 10 doctoral candidates will be trained as the next generation of gene therapy innovators and research leaders both in academia and industry.