AstraZeneca have a bold vision to deliver 20 new medicines, become an $80 billion company, and become carbon negative by the year 2030. A key part of doing this is being able to identify the right molecules through investing in next generation drug discovery platforms.
Matthew Burrell, Associate Director at AstraZeneca, leads a team working on their biologic generation platforms called BETXpress (Biologics Expression Team Express). The goal of the BETXpress team is to drive innovative solutions for the rapid generation of biologics. It started around five years ago in Cambridge, UK, and has since significantly evolved and expanded across the globe with sites in the US.
To be able to identify the right molecules, AstraZeneca have developed two next-generation discovery platforms: First is their machine learning-driven antibody and biologics deep screening platform; Second is B cell miner, AstraZeneca’s next generation in vivo platform. Both of these platforms deliver large panels of potential hits.
From there, the BETXpress team work on generating biologics for these hits in the appropriate format. They receive panels of hundreds of antibody sequences, take them through sequence design, followed by high throughput cloning, expression, purification, and QC. These then get transferred to the downstream team for high-throughput profiling. Key considerations at this stage include developability, accelerated stability, and non-specific binding.
To further increase the throughput, the team have developed an integrated automation platform which integrates liquid handlers with a robotic arm and advanced scheduling software. This platform increased their cloning capacity, reduced turnaround time, and improved robustness.
Once the cloning process is complete, the sequence verified plasmids go into their automated transfection process using their in-house G22 cell line before a ten day incubation. The biologics are then harvested and purified using an automated PhyTip-based method. Finally, the team measure the concentration of the purified molecules and run a UP-SEC for quality control.
