At Twist, we have developed a disruptive DNA synthesis platform to industrialize the engineering of biology. To match our capacity in generating antibody libraries, we use the Carterra LSA for screening and characterization. Its high throughput capabilities match our highly automated antibody production workflow and shift analytics upstream to the very start of our antibody production. We routinely generate binding kinetics on hundreds of clones in parallel, directly from crude antibody or purified samples using minimal sample. Additionally, epitope binning studies on large panels of antibodies are now possible early in a program, allowing us to assess the epitope coverage of our libraries quickly and identify clones with uniquely desirable binding properties.
Carterra’s LSA high throughput SPR (Surface Plasmon Resonance) instrument is an excellent tool to monitor new genotypes and to generate data to demonstrate that the transgenic animals are immunologically robust. ELISAs only provided a crude binary measure whereas epitope binning data produced on the LSA gives us a detailed picture of the epitope landscape of our antibody libraries quickly using crude samples. Having a platform which can give you not just specificity but also binding kinetics and allows you to rank clones at a stage where you only have small volumes is very amenable to high-throughput antibody discovery.
Antibody screening, characterization and epitope binning is a critical part of our therapeutic antibody discovery and development process. When we only used a BLI-based (biolayer interferometry) Octet system we were not able to perform full high-throughput kinetic analysis of unpurified or partially purified extracts or epitope binning on a large number of antibodies. The Carterra technology changed that and gave us the ability to perform very sensitive high-throughput full-kinetic analysis of unpurified bacterial extracts.
Our plan is to develop multiple antibodies against each of the cell surface proteins. Importantly, the synthetic recombinant antibodies that we plan to make will be an immortal resource for biomedical research. We will be honest and open about our endeavor so scientists will be able to draw rational conclusions about our work. Since there are about 5-6000 human cell surface and secreted proteins, that means we could be producing tens of thousands of new antibodies. A key part is to look at how well these antibodies bind, to rank them kinetically, to check specificity, and to perform epitope binning to define their binding epitopes. The LSA has the throughput to test large numbers of antibodies quickly, and is really good at epitope binning, which other systems do not seem to do as well. Since animals are not used in our recombinant approach, highly conserved epitopes can be targeted and the process can be turned around faster than traditional hybridoma technologies.
Early-stage characterization of the epitope landscape is critical for us to move the right therapeutic antibody candidates forward, without missing a potential blockbuster. Carterra’s LSA provides the greatest epitope binning capacity available in the biosensor space and it is enabling a paradigm shift here. We know a lot more, sooner, and that makes us more efficient and more productive.
Our LSA is up and running. The first install in Washington State! We’re excited to use it to speed up our therapeutic discovery process.
A major bottleneck in the kinetic and affinity characterization of therapeutic monoclonal antibodies binding to their antigens has been that SPR technology is low throughput. The Carterra LSA provides a significant increase in throughput for accurate determination of binding kinetics and affinities to help make lead choices much earlier in the discovery process. Another crucial high-throughput application long desired in antibody discovery is the ability to epitope bin large panels of antibodies. The Carterra LSA fulfills this need by allowing epitope binning of 384 antibodies.