By leveraging its unique tools and in vivo and in vitro technologies, Twist Biosciences centres on uncovering paths in antibody discovery. Radha Parmar, Senior Science and Technology Specialist at Twist Biosciences presented a case study on how they used an in-silico approach to discovery. Twist Bioscience uses phosphoramidite-based chemistry to miniaturize DNA synthesis onto a silicon platform, allowing the production of millions of oligos with base-by-base precision.
To effectively and quickly process antibody production, they have developed software that facilitates high-throughput processing. The express genes workflow speeds up the antibody production workflow. Customers input sequences which are sent to Twist Biosciences and the purified antibodies are ready to ship in just 10 business days. Parmar added that they examine cell lines for HEK 293 transfections and CHO cell lines.
In terms of supporting those in the antibody discovery space and antibody optimisation space, the team has many industry-leading tools and technologies under one roof. For repertoire generation, they often create custom libraries for customers. Parmar stated: “Our synthesis platform that allows us to do this whereby having base by base precision when we're building oligos, we can absolutely replicate designs that people have of naive discovery libraries, for example, and provide libraries of 10 billion variants in this space.”
A specific study used a GPCR target C5A receptor which is a difficult target that is important in the immune-oncology space where there are not enough candidates. Twist applied an in silico approach alongside immunisation and library-based discovery to generate antibody candidates. Neural networks identified druggable epitopes, leading to the design of 10,000 potential antibody structures. Using machine learning-based filtering and phage display, the team refined these candidates, ultimately identifying functional leads with improved potency through further optimisation.
The company has introduced Multiplex Gene Fragments, Multiplex gene fragments, allowing the creation of defined variant libraries for AIML-based affinity maturation, enhancing the precision and efficiency of antibody optimization. Through collaborations with external computational partners, Twist enhances its ability to predict epitopes and optimize antibody structures efficiently. Overall, Twist stands out with its high-quality, scalable, and cost-effective solutions while continually refining its workflows to further reduce turnaround times.
