Leveraging synthetic Library of Libraries to enable effective antibody discovery against high-impact targets

Using Twist’s high-throughput DNA synthesis platform, multiple high diversity synthetic antibody libraries have been built to serve as powerful tools for antibody discovery. Leveraging these highly diverse libraries, we have been able to identify high-affinity antibody candidates for a variety of targets. Here we demonstrate the antibody discovery process for 6 cytokine or immunomodulatory protein targets. This process spans constructing synthetic antibody libraries, using phage display to pan libraries against biotinylated protein targets, and screening for lead candidates through ELISA binding assays and NGS enrichment tracking. Utilizing a high-throughput approach, candidates are reformatted into full length IgG or VHH-Fc; the resulting monoclonal antibodies are then validated through SPR and cell-based assays. Many high affinity candidates with ranges of picomolar to nanomolar binding were identified for the six targets, demonstrating the efficacy of this discovery process.